rifampin and Neoplasms

Since many drugs are cytochrome P450 (CYP)-3A4 substrates, it has become common practice to assess drug-drug interaction (DDI) potential with a CYP3A4 inhibitor (ketoconazole) or inducer (rifampicin) in early drug development. Such an evaluation is relevant to anticancer drugs with metabolism governed by CYP3A4. DDIs with rifampicin are complex, involving other physiological mechanisms that may impact overall pharmacokinetics. Our objective was to study and delineate such mechanisms for oral versus intravenous anticancer drugs. We hypothesized that DDIs between anticancer drugs and rifampicin were primarily driven by CYP3A4 induction. This hypothesis was proven for the oral anticancer drugs; however, in some cases, other intrinsic mechanisms such as P-glycoprotein (Pgp)/UDP glucuronosyl transferase (UGT) induction and transporter inhibition may have played an important role alongside the induced CYP3A4 enzymes. The hypothesis that CYP3A4 induction would decrease drug exposure appeared paradoxical for intravenous romidepsin and-to a somewhat lesser extent-for cabazitaxel. In light of this dilemma in the interpretation of the pharmacokinetic data with rifampicin, several questions require further consideration. Given the complexity and paradoxical effects arising with DDIs with rifampicin, the continued preference for rifampicin as CYP3A4 inducer needs immediate re-appraisal.

Topics: Administration, Intravenous; Antineoplastic Agents; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Drug Discovery; Drug Interactions; Drug Therapy, Combination; Enzyme Induction; Humans; Neoplasms; Rifampin

Modulation of P-glycoprotein (Pgp)-mediated transport has significant pharmacokinetic implications for Pgp substrates. Pharmacokinetic alterations may be at the systemic (blood concentrations), regional (organ or tissue concentrations), or local (intracellular concentrations) level. Regardless of the particular location of Pgp modulation, changes in substrate pharmacokinetics will have the potential to alter the magnitude and duration of pharmacologic effect (pharmacodynamics). It is important to understand each of the aspects of Pgp modulation for a given Pgp substrate in order to predict the degree to which Pgp modulation may affect that substrate, to minimize untoward effects associated with that modulation, or to exploit that modulation for specific therapeutic advantage.

Topics: Analgesics, Opioid; Animals; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Transport; Blood-Brain Barrier; Dexamethasone; Drug Resistance, Neoplasm; Enzyme Inhibitors; Glucocorticoids; Humans; Intestinal Absorption; Neoplasms; Rifampin; Tissue Distribution

High-dose interleukin-2 (HDIL-2) has proven to be an effective treatment for metastatic renal cell carcinoma and melanoma. Previous studies have shown an increase in catheter-related bacteremia (CRB) in patients on HDIL-2. The primary objective of this study was to evaluate the effectiveness of minocycline and rifampin-coated catheters (M/R-C) in reducing CRB in cancer patients on HDIL-2. This was a retrospective study where non-coated catheters (NC-C) and M/R-C were used for the administration of HDIL-2 before and after December 2004, respectively. Data collected included demographics, cancer type, catheter type, antibiotic prophylaxis, and infection rates. A total of 107 episodes of catheter use for HDIL-2 were evaluated in 78 patients (30 episodes in patients with M/R-C vs. 77 with NC-C). A total of nine episodes of CRB were identified, all in patients with NC-C (M/R-C 0% vs. NC-C 12%; p=0.06). The median time to bacteremia was 11 days (range 1-315 days). A log-rank test showed a trend that the M/R-C group had lower probability of getting CRB than the NC-C group (p=0.06). The use of M/R-C in patients on HDIL-2 therapy for advanced melanoma and renal cell carcinoma may have reduced the risk of CRB to nil. CRB still occurred despite antibiotic prophylaxis in patients with NC-C.

Topics: Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Female; Humans; Interleukin-2; Male; Middle Aged; Minocycline; Neoplasms; Rifampin; Treatment Outcome

In vertebrates, the glucuronidation of small lipophilic agents is catalyzed by the endoplasmic reticulum UDP-glucuronosyltransferases (UGTs). This metabolic pathway leads to the formation of water-soluble metabolites originating from normal dietary processes, cellular catabolism, or exposure to drugs and xenobiotics. This classic detoxification process, which led to the discovery nearly 50 years ago of the cosubstrate UDP-glucuronic acid (19), is now known to be carried out by 15 human UGTs. Characterization of the individual gene products using cDNA expression experiments has led to the identification of over 350 individual compounds that serve as substrates for this superfamily of proteins. This data, coupled with the introduction of sophisticated RNA detection techniques designed to elucidate patterns of gene expression of the UGT superfamily in human liver and extrahepatic tissues of the gastrointestinal tract, has aided in understanding the contribution of glucuronidation toward epithelial first-pass metabolism. In addition, characterization of the UGT1A locus and genetic studies directed at understanding the role of bilirubin glucuronidation and the biochemical basis of the clinical symptoms found in unconjugated hyperbilirubinemia have uncovered the structural gene polymorphisms associated with Crigler-Najjar's and Gilbert's syndrome. The role of the UGTs in metabolism and different disease states in humans is the topic of this review.

Topics: Autoimmunity; Chromosome Mapping; Glucuronides; Glucuronosyltransferase; Humans; Hyperbilirubinemia; Neoplasms; Steroids; Terminology as Topic

Pamiparib is an investigational, selective, oral poly(ADP-ribose) polymerase 1/2 (PARP1/2) inhibitor that has demonstrated PARP-DNA complex trapping and CNS penetration in preclinical models, as well as preliminary anti-tumor activity in early-phase clinical studies. We investigated whether the single-dose pharmacokinetic (PK) profile of pamiparib is altered by coadministration of a strong CYP3A inducer (rifampin) or a strong CYP3A inhibitor (itraconazole) in patients with solid tumors.. In this open-label, phase 1 study, adults with advanced solid tumors received either oral pamiparib 60 mg (days 1 and 10) and once-daily oral rifampin 600 mg (days 3-11) or oral pamiparib 20 mg (days 1 and 7) and once-daily oral itraconazole 200 mg (days 3-8). Primary endpoints included pamiparib maximum observed concentration (C. Rifampin coadministration did not affect pamiparib C. Pamiparib plasma exposure was reduced 38-43% with rifampin coadministration but was unaffected by itraconazole coadministration. Pamiparib dose modifications are not considered necessary when coadministered with CYP3A inhibitors. Clinical safety and efficacy data will be used with these results to recommend dose modifications when pamiparib is coadministered with CYP3A inducers.

Topics: Adult; Aged; Area Under Curve; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Female; Fluorenes; Humans; Itraconazole; Male; Middle Aged; Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Rifampin

Topics: Adult; Aged; Aged, 80 and over; Cytochrome P-450 CYP3A; Drug Administration Schedule; Drug Interactions; Female; Humans; Male; Middle Aged; Mutation; Neoplasms; Proto-Oncogene Proteins B-raf; Rifampin; Vemurafenib

At clinically relevant ixazomib concentrations, in vitro studies demonstrated that no specific cytochrome P450 (CYP) enzyme predominantly contributes to ixazomib metabolism. However, at higher than clinical concentrations, ixazomib was metabolized by multiple CYP isoforms, with the estimated relative contribution being highest for CYP3A at 42%. This multiarm phase 1 study (Clinicaltrials.gov identifier: NCT01454076) investigated the effect of the strong CYP3A inhibitors ketoconazole and clarithromycin and the strong CYP3A inducer rifampin on the pharmacokinetics of ixazomib. Eighty-eight patients were enrolled across the 3 drug-drug interaction studies; the ixazomib toxicity profile was consistent with previous studies. Ketoconazole and clarithromycin had no clinically meaningful effects on the pharmacokinetics of ixazomib. The geometric least-squares mean area under the plasma concentration-time curve from 0 to 264 hours postdose ratio (90%CI) with vs without ketoconazole coadministration was 1.09 (0.91-1.31) and was 1.11 (0.86-1.43) with vs without clarithromycin coadministration. Reduced plasma exposures of ixazomib were observed following coadministration with rifampin. Ixazomib area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration was reduced by 74% (geometric least-squares mean ratio of 0.26 [90%CI 0.18-0.37]), and maximum observed plasma concentration was reduced by 54% (geometric least-squares mean ratio of 0.46 [90%CI 0.29-0.73]) in the presence of rifampin. The clinical drug-drug interaction study results were reconciled well by a physiologically based pharmacokinetic model that incorporated a minor contribution of CYP3A to overall ixazomib clearance and quantitatively considered the strength of induction of CYP3A and intestinal P-glycoprotein by rifampin. On the basis of these study results, the ixazomib prescribing information recommends that patients should avoid concomitant administration of strong CYP3A inducers with ixazomib.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Boron Compounds; Clarithromycin; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Female; Glycine; Humans; Ketoconazole; Male; Middle Aged; Models, Biological; Neoplasms; Proteasome Inhibitors; Rifampin

Topics: Adult; Biphenyl Compounds; Computer Simulation; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Female; Healthy Volunteers; Humans; Ketoconazole; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Neoplasms; Pyridines; Rifampin; Smoothened Receptor; Time Factors; Young Adult

Two multicenter, single-arm, single-infusion, open-label studies were conducted to evaluate the effect of ketoconazole (a strong CYP3A inhibitor) or rifampin (a strong CYP3A inducer) daily for 5 days on the pharmacokinetics (PK) and safety of romidepsin (8 mg/m(2) intravenous 4-hour infusion for the ketoconazole study or a 14 mg/m(2) intravenous 4-hour infusion for the rifampin study) in patients with advanced cancer. Romidepsin coadministered with ketoconazole (400 mg) or rifampin (600 mg) was not bioequivalent to romidepsin alone. With ketoconazole, the mean romidepsin AUC and Cmax were increased by approximately 25% and 10%, respectively. With rifampin, the mean romidepsin AUC and Cmax were unexpectedly increased by approximately 80% and 60%, respectively; this is likely because of inhibition of active liver uptake. For both studies, romidepsin clearance and volume of distribution were decreased, terminal half-life was comparable, and median Tmax was similar. Overall, the safety profile of romidepsin was not altered by coadministration with ketoconazole or rifampin, except that a higher incidence and greater severity of thrombocytopenia was observed when romidepsin was given with rifampin. The use of romidepsin with rifampin and strong CYP3A inducers should be avoided. Toxicity related to romidepsin exposure should be monitored when romidepsin is given with strong CYP3A inhibitors.

Topics: Adult; Aged; Aged, 80 and over; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Depsipeptides; Drug Interactions; Female; Humans; Ketoconazole; Male; Middle Aged; Neoplasms; Rifampin

Navitoclax, a first-in-class small molecule Bcl-2 family inhibitor, is metabolized in vitro by the hepatic microsomal cytochrome P450 (CYP) enzymes CYP3A4. Drugs that affect CYP3A4 may therefore have an impact on the pharmacological profile of navitoclax. This study evaluated the effects of co-administration of a potent CYP3A4 inducer rifampin on the pharmacokinetic and safety profiles of navitoclax.. This open-label, fixed-sequence, 2-period study was performed in twelve subjects with non-haematologic or haematologic malignancy that was relapsed or refractory to standard therapy. A 7-day washout period separated the two treatment periods. On Study Day 1 and Day 8, subjects received a single 250 mg oral dose of navitoclax. Rifampin 600 mg was administrated once daily (QD) on Study Day 4 through Day 10. Blood samples for navitoclax assay were collected prior to dosing (0 h) and at a series of time points through 72 h after dosing on Study Day 1 and Day 8.. Co-administration of a single 250 mg dose of navitoclax with 600 mg QD doses of rifampin had a negligible effect on the maximum plasma concentration (Cmax ) of navitoclax [ratio of geometric least square means: 0·84 (90% CI: 0·61-1·16)] but moderately decreased the area under the plasma concentration-time curve (AUC) of navitoclax [ratio of geometric least square means: 0·59 (90% CI: 0·44-0·80)]. Rifampin did not affect the half-life of navitoclax. Co-administration of rifampin did not appear to significantly change the safety profile of navitoclax in the limited number of patients evaluated in this study.. Co-administration navitoclax with rifampin moderately decreased navitoclax AUC, which could be partly due to the induction effect of rifampin on CYP3A4. Further assessment on the mechanism of drug interaction is warranted.

Topics: Aged; Aged, 80 and over; Aniline Compounds; Antineoplastic Agents; Area Under Curve; bcl-X Protein; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Drug Interactions; Female; Half-Life; Humans; Male; Middle Aged; Neoplasms; Proto-Oncogene Proteins c-bcl-2; Rifampin; Sulfonamides

To evaluate the pharmacokinetics, safety and survival of trabectedin, metabolized primarily by cytochrome P450 (CYP)3A4 enzyme, when coadministered with rifampin (CYP3A4 inducer) or ketoconazole (CYP3A4 inhibitor) in adult patients with advanced solid tumors.. Two phase 1/2a, 2-way crossover studies were conducted. For rifampin study, 12 patients were randomized (1:1) to sequence of a cycle of trabectedin (1.3 mg/m(2), 3 h, i.v.) coadministered with rifampin (600 mg/day, 6-days), and a cycle of trabectedin monotherapy (1.3 mg/m(2), 3 h, i.v.). In ketoconazole study, eight patients were randomized (1:1) to sequence of a cycle of trabectedin (0.58 mg/m(2), 3 h, i.v.) coadministered with ketoconazole (200 mg, twice-daily, 15-doses), and a cycle of trabectedin monotherapy (1.3 mg/m(2), 3 h, i.v.).. The systemic exposure (geometric means) of trabectedin was decreased [22% (C max) and 31% (AUClast)] with rifampin coadministration and increased [22% (C max) and 66% (AUClast)] with ketoconazole coadministration. This correlated with an increased clearance with rifampin (39.6-59.8 L/h) and a decreased clearance with ketoconazole (20.3-12.0 L/h). Consistent with earlier studies, the most common (≥40%) treatment-emergent adverse events in both studies were nausea, vomiting, diarrhea, hepatic function abnormal, anemia, neutropenia, thrombocytopenia and leukopenia.. Coadministration of rifampin or ketoconazole altered the pharmacokinetics of trabectedin, but no new safety signals were observed. Coadministration of trabectedin with potent CYP3A4 inhibitors or inducers should be avoided if possible. If coadministration of trabectedin with a strong CYP3A4 inhibitor is required, close monitoring for toxicities is recommended, so that appropriate dose reductions can be instituted as warranted.

Topics: Adult; Antineoplastic Agents; Cytochrome P-450 CYP3A; Dioxoles; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Antagonism; Drug Monitoring; Drug Screening Assays, Antitumor; Drug-Related Side Effects and Adverse Reactions; Enzyme Activators; Enzyme Inhibitors; Female; Humans; Ketoconazole; Male; Metabolic Clearance Rate; Neoplasm Invasiveness; Neoplasm Staging; Neoplasms; Rifampin; Tetrahydroisoquinolines; Trabectedin; Treatment Outcome

Cabazitaxel is primarily metabolized by CYP3A. This study evaluated the impact of moderate/strong CYP3A inhibitors [aprepitant (Study Part 2); ketoconazole (Study Part 3)] or strong CYP3A inducers [rifampin (Study Part 4)] on the pharmacokinetics of cabazitaxel.. Adult patients received IV cabazitaxel/cisplatin 15/75 mg/m(2) on Day 1 of 3-week cycles (5/75 mg/m(2) in Cycles 1 and 2 of Part 3 to allow a safety margin to the cabazitaxel MTD). Patients received repeated oral doses of aprepitant, ketoconazole or rifampin before/during Cycle 2. Cabazitaxel clearance was the primary endpoint; clearance and area under the plasma concentration-time curve (AUC) were normalized to body surface area and dose, respectively.. The PK population included 13 (Part 2), 23 (Part 3) and 21 patients (Part 4). Repeated aprepitant administration did not affect cabazitaxel clearance [geometric mean ratio (GMR) 0.98; 90 % confidence interval (CI) 0.80-1.19]. Repeated ketoconazole administration resulted in 20 % decrease in cabazitaxel clearance (GMR 0.80; 90 % CI 0.55-1.15), associated with 25 % increase in AUC (GMR 1.25; 90 % CI 0.86-1.81). Repeated rifampin administration resulted in 21 % increase in cabazitaxel clearance (GMR 1.21; 90 % CI 0.95-1.53), associated with 17 % decrease in AUC (GMR 0.83; 90 % CI 0.65-1.05). The GMR of AUC0-24 with rifampin administration was 1.09 (90 % CI 0.9-1.33), suggesting that rifampin had a low impact during the initial phases of cabazitaxel elimination. Safety findings were consistent with previous results.. Cabazitaxel pharmacokinetics are modified by drugs strongly affecting CYP3A. Co-administration of cabazitaxel with strong CYP3A inhibitors or inducers should be avoided.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Area Under Curve; Cisplatin; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inducers; Drug Interactions; Female; Humans; Ketoconazole; Male; Middle Aged; Morpholines; Neoplasms; Rifampin; Taxoids

To investigate any effect of a CYP3A4 inhibitor (ketoconazole) or inducer (rifampicin) on cediranib steady-state pharmacokinetics in patients with advanced solid tumours.. In two Phase I, open-label trials, patients received once-daily oral doses of cediranib alone [20 mg (ketoconazole study); 45 mg (rifampicin study)] for 7 days followed by cediranib at the same dose with ketoconazole 400 mg/day for 3 days or once-daily rifampicin 600 mg/day for 7 days, respectively. Patients then continued to receive once-daily cediranib.. In the ketoconazole study, 46 patients were dosed; 38 were evaluable for C (ss,max), 36 for AUC(ss). gMean AUC(ss) and C (ss,max) for cediranib 20 mg increased by 21 % (94 % CI 9-35 %) and 26 % (94 % CI 10-43 %), respectively, in the presence of ketoconazole. In the rifampicin study, 64 patients were dosed; 44 were evaluable for C (ss,max) and 41 for AUC(ss). gMean AUC(ss) and C (ss,max) for cediranib 45 mg decreased by 39 % (90 % CI 34-43 %) and 23 % (90 % CI 16-30 %), respectively, in the presence of rifampicin. gMean ratios for AUC(ss) and C (ss,max) were >1 for ketoconazole and <1 for rifampicin and CIs were outside the pre-specified equivalence boundaries, indicating a statistically significant effect. Significant inter-patient variability in cediranib AUC(ss) and C (ss,max) was observed. The safety profile of cediranib was similar to that reported previously.. Co-administration of ketoconazole or rifampicin had statistically significant effects on steady-state pharmacokinetics of cediranib in patients with advanced solid tumours. Therefore, caution is advised when administering cediranib with potent enzyme inhibitors or inducers.

Topics: Adult; Aged; Area Under Curve; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Humans; Ketoconazole; Middle Aged; Neoplasms; Quinazolines; Receptors, Vascular Endothelial Growth Factor; Rifampin; Young Adult

Antimicrobial central venous catheters are discussed as a device to reduce catheter-related infections. Previously we have reported a study with 223 adult surgical patients randomized to receive either a rifampicin-miconazole-loaded central venous catheter (CVC) (n=118) or a standard CVC (n=105). The antimicrobial CVC was shown to reduce catheter colonization (CC) and catheter-related local infection (CRI) significantly even at long-term catheterization. Here, we present further evaluation of the study focusing on possible benefits for high-risk patients. Subgroup analyses showed a pronounced reduction of CC and CRI in male, overweight and oncology patients. Important covariates were skin colonization for CC and oncological disease for CRI. Odds ratio (OR) for reducing CC was 0.076 (95% CI: 0.016-0.360) and CRI was reduced from 26% to 2.3% (p=0.001) in the cancer subgroup. Ex vivo long-term antimicrobial activity of modified catheters exceeded 4 weeks.. Immunocompromized patients suffering from cancer, transplantation, and dialysis patients with a long-term vascular access may mostly benefit from rifampicin-miconazole-releasing catheters.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibiotics, Antitubercular; Antifungal Agents; Bacterial Infections; Catheterization, Central Venous; Catheters, Indwelling; Coated Materials, Biocompatible; Equipment Contamination; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Miconazole; Middle Aged; Mycoses; Neoplasms; Rifampin; Risk Factors; Young Adult

Gefitinib (IRESSA, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, has been approved in several countries for the treatment of advanced non-small-cell lung cancer. Preclinical studies were conducted to determine the cytochrome P450 (CYP) isoenzymes involved in the metabolism of gefitinib and to evaluate the potential of gefitinib to cause drug interactions through inhibition of CYP isoenzymes. Based on these findings, three clinical studies were carried out to investigate pharmacokinetic drug interactions in vivo with gefitinib.. In preclinical studies radiolabelled gefitinib was incubated with: (i) hepatic microsomal protein in the presence of selective CYP inhibitors; and (ii) expressed CYP enzymes. Human hepatic microsomal protein was incubated with selective CYP substrates in the presence of gefitinib. Clinical studies were all phase I, open-label, single-centre studies; two had a randomised, two-way crossover design and the third was nonrandomised. The first and second studies investigated the pharmacokinetics of gefitinib in the presence of a potent CYP3A4 inducer (rifampicin [rifampin]) or inhibitor (itraconazole) in healthy male volunteers. The third study investigated the effects that gefitinib had on the pharmacokinetics of metoprolol, a CYP2D6 substrate, in patients with solid tumours.. The results of preclinical studies demonstrated that CYP3A4 is involved in the metabolism of gefitinib and that gefitinib is a weak inhibitor of CYP2D6 activity. In clinical studies when gefitinib was administered in the presence of rifampicin, geometric mean (gmean) maximum concentration and area under the plasma concentration-time curve (AUC) were reduced by 65% and 83%, respectively; these changes were statistically significant. When gefitinib was administered in the presence of itraconazole, gmean AUC increased by 78% and 61% at gefitinib doses of 250 and 500 mg, respectively; these changes also being statistically significant. Coadministration of metoprolol with gefitinib resulted in a 35% increase in the metoprolol area under plasma concentration-time curve from time zero to the time of the last quantifiable concentration; this change was not statistically significant. There was no apparent change in the safety profile of gefitinib as a result of coadministration with other agents.. Although CYP3A4 inducers may reduce exposure to gefitinib, further work is required to define any resultant effect on the efficacy of gefitinib. Exposure to gefitinib is increased by coadministration with CYP3A4 inhibitors, but since gefitinib is known to have a good tolerability profile, a dosage reduction is not recommended. Gefitinib is unlikely to exert a clinically relevant effect on the pharmacokinetics of drugs that are dependent on CYP2D6-mediated metabolism for their clearance, but the potential to increase plasma concentrations should be considered if gefitinib is coadministered with CYP2D6 substrates that have a narrow therapeutic index or are individually dose titrated.

Topics: Adolescent; Adult; Antineoplastic Agents; Cross-Over Studies; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Combinations; Drug Interactions; Enzyme Induction; Enzyme Inhibitors; Female; Gefitinib; Humans; Itraconazole; Male; Metoprolol; Microsomes, Liver; Middle Aged; Neoplasms; Quinazolines; Rifampin

To evaluate the efficacy of long-term nontunneled silicone catheters impregnated with minocycline and rifampin (M-R) in reducing catheter-related bloodstream infections.. This prospective, randomized, double-blind clinical trial was conducted at M.D. Anderson Cancer Center, a tertiary care hospital in Houston, TX. All patients in the trial had a malignancy.. Between September 1999 and May 2002, 356 assessable catheters were used: 182 M-R and 174 nonimpregnated. The patients' characteristics were comparable between the two study groups. The mean (+/- standard deviation) duration of catheterization with M-R catheters was comparable to that of nonimpregnated catheters (66.21 +/- 30.88 v 63.01 +/- 30.80 days). A total of 17 catheter-related bloodstream infections occurred during the course of the study. Three were associated with the use of M-R catheters and 14 were associated with the nonimpregnated catheters, with a rate of catheter-related bloodstream infection of 0.25 and 1.28/1,000 catheter-days, respectively (P = .003). Gram-positive cocci accounted for the majority of the organisms causing the infections. There were no allergic reactions associated with M-R catheters.. Long-term nontunneled central venous catheters impregnated with minocycline and rifampin are efficacious and safe in reducing catheter-related bloodstream infections in cancer patients.

Topics: Anti-Bacterial Agents; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Double-Blind Method; Female; Humans; Male; Middle Aged; Minocycline; Neoplasms; Prospective Studies; Rifampin; Silicones

To determine whether the addition of rifampin to a quinolone-based antibacterial prophylactic regimen in patients undergoing high-dose chemotherapy (HDC) with peripheral-blood stem-cell transplantation (PBSCT) decreases the incidence of neutropenia and fever, Gram-positive bacteremia, and infection-related morbidity.. Patients with solid tumors undergoing HDC with PBSCT were randomized to receive prophylactic antibiotics with either ciprofloxacin 500 mg orally every 8 hours or the same ciprofloxacin regimen with rifampin 300 mg orally every 12 hours. Prophylaxis was started 48 hours before stem-cell reinfusion. Patients were monitored to document the occurrence of neutropenia and fever, incidence and cause of bacterial infection, time to onset and duration of fever, requirement for intravenous antimicrobials, and length of hospital admission.. Sixty-five patients were randomized to receive ciprofloxacin and 65 to receive ciprofloxacin plus rifampin, and from these groups, 62 and 61 were assessable, respectively. The proportion of patients who developed neutropenia and fever was 87% in the group treated with ciprofloxacin and 78% in the group treated with ciprofloxacin and rifampin (P =.25). Although there was a trend toward a reduction in the overall incidence of bacteremia (12 v 4 patients), and Gram-positive bacteremia (8 v 2 patients) with the addition of rifampin, none of these comparisons was statistically significant (P =.05 and P =.09, respectively).. The results of this study, which demonstrate that rifampin does not improve ciprofloxacin antibacterial prophylaxis in cancer patients undergoing HDC with PBSCT support but that it does increase the occurrence of undesirable side effects, do not support the routine use of rifampin in this setting.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Antineoplastic Agents; Ciprofloxacin; Drug Therapy, Combination; Female; Fever; Gram-Positive Bacterial Infections; Hematopoietic Stem Cell Transplantation; Humans; Male; Neoplasms; Neutropenia; Prospective Studies; Rifampin; Statistics, Nonparametric; Treatment Outcome

We compared ciprofloxacin alone with ciprofloxacin plus rifampin (C + R) as a prophylactic antibacterial regimen for 40 patients with solid tumors treated with high-dose chemotherapy and autologous stem cell transplantation support. No differences were found between groups in the time elapsed to the onset of fever, incidence of febrile episodes, amphotericin B use, and length of hospital stay. However, C + R combination prophylaxis significantly reduced the incidence of gram-positive bacteremia (five versus zero episodes) but was associated with a higher incidence of drug-related side effects.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Antineoplastic Combined Chemotherapy Protocols; Ciprofloxacin; Drug Therapy, Combination; Female; Fever; Gram-Positive Bacterial Infections; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Rifampin

Clostridium difficile infection (CDI) is a leading cause of healthcare-associated diarrhea worldwide. In this study, risk factors associated with the development of severe-complicated and recurrent outcomes in CDI patients in different age groups, including the non-elderly, were assessed in a third-level hospital.. CDI cases were detected by clinical data and polymerase-chain-reaction (PCR). Clinical, demographic, epidemiological, and microbiological risk factors for CDI were evaluated.. During the study period, 248 out of 805 patients with nosocomial diarrhea were diagnosed with CDI and the majority were severe-complicated cases (87.90%). Female gender (OR 3.19, 95% CI 1.19-8.55, p = 0.02) and lymphoma (OR 3.95, 95% CI 1.03-15.13, p = 0.04) were risk factors for severe-complicated CDI. Mature adulthood (51-60 years) (OR 5.80, 95% CI 1.56-21.62, p = 0.01), previous rifampicin use (OR 7.44, 95% CI 2.10-26.44, p = 0.00), and neoplasm (solid malignant neoplasm or hematological malignancies) (OR 4.12, 95% CI 1.01-16.83, p = 0.04) were risk factors for recurrent infection. Autoimmune disorders (OR 6.62, CI 95% 1.26-34.73, p = 0.02), leukemia (OR 4.97, 95% CI 1.05-23.58, p = 0.04), lymphoma (OR 3.79, 95% CI 1.03-12.07, p = 0.04) and previous colistin treatment (OR 4.97, 95% CI 1.05-23.58, p = 0.04) were risk factors for 30-day mortality.. Newly identified risk factors for recurrent CDI were rifampicin treatment and age between 51 and 60 years; colistin treatment was identified as a risk factor for 30-day mortality. Previously identified risk factors for severe-complicated CDI were confirmed, but with a major impact on non-elderly patients.

Topics: Adult; Clostridioides difficile; Clostridium; Clostridium Infections; Colistin; Diarrhea; Female; Hospitals, Teaching; Humans; Mexico; Middle Aged; Neoplasms; Rifampin; Risk Factors

This study aimed to investigate the drug-drug interactions of ponatinib with strong, moderate, or weak CYP3A4 inhibitors/inducers by developing physiologically based pharmacokinetic (PBPK) models.. The PBPK model of ponatinib accurately represented its oral pharmacokinetics. It also reasonably predicted its pharmacokinetics when combined with ketoconazole and rifampicin. No weak to strong CYP3A4 inhibitor combinations significantly increased the AUC of ponatinib. However, the strong CYP3A4 inducers rifampicin (oral, 600 mg QD) and phenytoin (oral, 100 mg TID) decreased AUC by 60-70% and 50%, respectively.. The PBPK model predicted a significant drug interaction when ponatinib was combined with a strong CYP3A4 inducer. Conversely, the combination with weak-to-strong CYP3A4 inhibitors did not suggest a drug interaction with ponatinib.

Topics: Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Humans; Imidazoles; Models, Biological; Neoplasms; Pyridazines; Rifampin

Osimertinib is a potent, highly selective, irreversible inhibitor of epidermal growth factor receptor (EGFR) and T790M resistance mutation. In vitro metabolism data suggested osimertinib is a substrate of cytochrome P450 (CYP)3A4/5, a weak inducer of CYP3A, and an inhibitor of breast cancer resistance protein (BCRP). A combination of in vitro data, clinical pharmacokinetic data, and drug-drug interaction (DDI) data of osimertinib in oncology patients were used to develop the physiologically based pharmacokinetic (PBPK) model and verify the DDI data of osimertinib. The model predicted the observed monotherapy concentration profile of osimertinib within 1.1-fold, and showed good predictability (within 1.7-fold) to the observed peak plasma concentration (C

Topics: Acrylamides; Aniline Compounds; Area Under Curve; Computer Simulation; Cytochrome P-450 CYP3A; Drug Dosage Calculations; Drug Interactions; Humans; Itraconazole; Models, Theoretical; Neoplasms; Rifampin; Rosuvastatin Calcium; Simvastatin

A population pharmacokinetic (PK) model was developed for cediranib to simulate cediranib exposure for different doses, including comedication with strong uridine glucuronosyl transferase/P-glycoprotein inducers such as rifampicin, in cancer patients.. Plasma concentrations and covariates from 625 cancer patients after single or multiple oral cediranib administrations ranging from 0.5 to 90 mg in 19 Phase I and II studies were included in the analysis. Stepwise covariate modelling was used to develop the population PK model. The final model was used to simulate cediranib exposure in cancer patients to evaluate cediranib target coverage and the need for dose adjustment for covariates or coadministration with rifampicin.. A two-compartment model with sequential zero- and first-order absorption and first-order elimination adequately described the cediranib concentration-time courses. Body weight and age were identified as having statistically significant impact on cediranib PK, but only <21% impact on AUC and maximum concentrations. Simulated lower bounds of 90% prediction interval or median of unbound cediranib concentrations after cediranib 15 or 20 mg exceeded the IC. No covariate was identified to require dose adjustment for cediranib. Cediranib exposure following 15 or 20 mg daily dose administration is adequate overall for inhibition of in vitro estimated vascular endothelial growth factor receptor-1, -2 and -3 activities. An increase in cediranib dose may be needed for cediranib coadministered with strong uridine glucuronosyl transferase/P-glycoprotein inducers such as rifampicin.

Topics: Administration, Oral; Adult; Age Factors; Aged; Aged, 80 and over; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; Body Weight; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Female; Glucuronosyltransferase; Humans; Inhibitory Concentration 50; Male; Middle Aged; Models, Biological; Neoplasms; Polypharmacy; Protein Kinase Inhibitors; Quinazolines; Rifampin; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factor Receptor-3; Young Adult

Erlotinib is approved for the treatment of non-small cell lung and pancreatic cancers, and is metabolized by CYP3A4. Inducers and inhibitors of CYP3A enzymes such as ritonavir and efavirenz, respectively, may be used as part of the highly active antiretroviral therapy drugs to treat patients with human immunodeficiency virus (HIV). When HIV patients with a malignancy need treatment with erlotinib, there is a potential of as-yet-undefined drug-drug interaction. We evaluated these interactions using human hepatocytes benchmarked against the interaction of erlotinib with ketoconazole and rifampin, the archetype cytochrome P450 inhibitor and inducer, respectively. Hepatocytes were treated with vehicle [0.1% dimethylsulfoxide, ritonavir (10 μM)], ketoconazole (10 μM), efavirenz (10 μM), or rifampin (10 μM) for 4 days. On day 5, erlotinib (5 μM) was incubated with the above agents for another 24-48 hours. Concentrations of erlotinib and O-desmethyl erlotinib were quantitated in collected samples (combined lysate and medium) using liquid chromatography and tandem mass spectrometry. The half-life (t(½)) of erlotinib increased from 10.6 ± 2.6 to 153 ± 80 and 23.9 ± 4.8 hours, respectively, upon treatment with ritonavir and ketoconazole. The apparent intrinsic clearance (C(Lint, app)) of erlotinib was lowered 16-fold by ritonavir and 1.9-fold by ketoconazole. Efavirenz and rifampin decreased t1/2 of erlotinib from 10.3 ± 1.1 to 5.0 ± 1.5 and 3.4 ± 0.2 hours, respectively. Efavirenz and rifampin increased the C(Lint, app) of erlotinib by 2.2- and 2-fold, respectively. Our results suggest that to achieve desired drug exposure, the clinically used dose (150 mg daily) of erlotinib may have to be significantly reduced (25 mg every other day) or increased (300 mg daily), respectively, when ritonavir or efavirenz is coadministered.

Topics: 14-alpha Demethylase Inhibitors; Adult; Aged; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Drug Interactions; Erlotinib Hydrochloride; Female; Half-Life; Hepatocytes; HIV Infections; HIV Protease Inhibitors; Humans; Ketoconazole; Male; Middle Aged; Neoplasms; Nucleic Acid Synthesis Inhibitors; Quinazolines; Rifampin; Ritonavir

Eribulin mesylate is a non-taxane microtubule dynamics inhibitor that was recently approved for treatment of metastatic breast cancer. The aim of this study was to determine the effect of rifampicin, a CYP3A4 inducer, on the plasma pharmacokinetics of eribulin in patients with solid tumours.. An open-label, non-randomized phase I study was carried out. Patients received intravenous 1.4 mg m(-2) eribulin mesylate on days 1 and 15 and oral rifampicin 600 mg on days 9 to 20 of a 28 day cycle. Pharmacokinetic sampling for determination of eribulin plasma concentrations was performed up to 144 h following administration. AUC(0,∞) and C(max) for eribulin exposure without or with co-administration of rifampicin were subjected to an analysis of variance (anova) and corresponding 90% confidence intervals (CI) were calculated. Subsequently, patients were allowed to continue eribulin mesylate treatment with 1.4 mg m(-2) eribulin mesylate on days 1 and 8 of a 21 day cycle. Also the adverse event profile and anti-tumour activity were assessed.. Fourteen patients were included and 11 patients were evaluable for pharmacokinetic analysis. Co-administration of rifampicin had no effect on single dose exposure to eribulin (geometric least square means ratio: AUC(0,∞) = 1.10, 90% CI 0.91, 1.34 and C(max) = 0.97, 90% 0.81, 1.17). The most common treatment-related grade ≥3 adverse events were grade 3 neutropenia (4/14, 29%), leucopenia and fatigue (both 3/14, 21%).. These results indicate that eribulin mesylate may be safely co-administered with compounds that are CYP3A4 inducers.

Topics: Administration, Oral; Adult; Aged; Antimitotic Agents; Area Under Curve; Asian People; Drug Interactions; Enzyme Inhibitors; Female; Furans; Humans; Ketones; Male; Microtubules; Middle Aged; Neoplasms; Rifampin; White People

Data are sparse on Mycobacterium tuberculosis infection among patients with cancer in Egypt. We sought to detect the presence of tuberculosis (TB) disease among patients with malignant conditions and suspected TB and to study the main risk factors. Also, we compared different diagnostic procedures and detected the antimicrobial susceptibility of M. tuberculosis isolates against rifampin and isoniazid. One hundred patients were included in this study, all of them had malignant conditions and were suspected by the clinicians of having TB. Identification of M. tuberculosis in different specimens was performed by smear microscopy, followed by Lowenstein-Jensen medium and Mycobacterium growth indicator tube (MGIT) cultures and artus(®) real-time PCR. In addition, an indirect MGIT anti-TB susceptibility test was carried out against rifampin and isoniazid. A total of 76% of studied cases were found to be TB positive. The frequencies of TB-positive cases in the bronchogenic, haematological and solid tumour malignancy groups were 21%, 25% and 30%, respectively. Significant differences between pulmonary and extrapulmonary TB in different malignancy groups were recorded. Real-time PCR showed the highest overall diagnostic efficiency. Multidrug-resistance of M. tuberculosis to both rifampin and isoniazid was detected in 28.6% of examined isolates. Infection in cancer patients with TB was significantly more often recorded among elderly patients and those suffering from poverty. Pulmonary TB is more common than extrapulmonary TB in patients with malignancy. Real-time PCR is the most accurate and rapid method for TB diagnosis. MGIT-rifampin resistance may be used as a reliable marker for detection of multidrug-resistant TB. Diagnosis and instituting treatment course for active or latent TB infection are crucial before starting anticancer therapy.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Bacteriological Techniques; Child; Drug Resistance, Bacterial; Egypt; Female; Humans; Isoniazid; Male; Middle Aged; Mycobacterium tuberculosis; Neoplasms; Prevalence; Real-Time Polymerase Chain Reaction; Rifampin; Risk Factors; Sensitivity and Specificity; Tuberculosis; Young Adult

Topics: Antineoplastic Agents; Antitubercular Agents; Drug Resistance, Multiple, Bacterial; Humans; Neoplasms; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant

To evaluate the impact of using central venous catheters (CVCs) impregnated with the combination of minocycline and rifampin on nosocomial bloodstream infections (BSIs), morbidity, and mortality in cancer patients in the ICU.. Prospective surveillance study consisting of the following two time periods: September 1997 through August 1998 (ie, fiscal year [FY] 1998); and from September 1998 through August 1999 (ie, FY 1999).. ICUs of a tertiary care hospital in Houston, TX.. Cancer patients in the medical ICU (MICU) and surgical ICU (SICU).. ICUs started using CVCs impregnated with the minocycline-rifampin combination at the beginning of FY 1999.. The rates of nosocomial BSIs and other patients' characteristics were compared for the two study periods to determine the impact of using the impregnated catheters in the ICU. Patients' characteristics, including antibiotic use, were comparable for the two study periods in both the MICU and the SICU. The rate of nosocomial BSIs in the MICU unit decreased from 8.3 to 3.5 per 1,000 patient-days (p < 0.01), and decreased in the SICU from 4.8 to 1.3 per 1,000 patient-days (p < 0.01) in FY 1999. Nosocomial vancomycin-resistant enterococcus (VRE) bacteremia also decreased significantly (p = 0.004). Length of stay in the MICU and SICU significantly decreased in FY 1999 (p < 0.01 and p = 0.03, respectively). The duration of hospitalization decreased for MICU and SICU patients (p = 0.06 and p < 0.01, respectively). The rate of catheter-related infections decreased from 3.1 to 0.7 per 1,000 patient-days in FY 1999 (p = 0.02). The decrease in infections resulted in net savings of at least $1,450,000 for FY 1999.. The use of antibiotic-impregnated CVCs in the MICU and SICU was associated with a significant decrease in nosocomial BSIs, including VRE bacteremia, catheter-related infections, and lengths of hospital and ICU stays.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Cause of Death; Child; Child, Preschool; Coated Materials, Biocompatible; Critical Care; Cross Infection; Drug Resistance, Multiple; Drug Therapy, Combination; Enterococcus; Female; Hospital Mortality; Humans; Male; Middle Aged; Minocycline; Neoplasms; Opportunistic Infections; Prospective Studies; Rifampin; Survival Rate; Texas; Vancomycin Resistance

Topics: Antibiotics, Antitubercular; Cholestasis; Drug Resistance, Microbial; Humans; Immunocompromised Host; Neoplasms; Pruritus; Rifampin

This study examines the effectiveness of prophylactic ciprofloxacin and rifampin following high-dose chemotherapy and autologous stem cell rescue (HDC/ ASCR). Specific endpoints included the incidence of fever, clinically documented infection, bacteremia, and readmission rates from an outpatient bone marrow transplant setting following infection or fever. A group of 97 patients receiving 134 cycles of HDC/ASCR were studied. Patients were given ciprofloxacin 750 mg p.o. twice daily and rifampin 300 mg p.o. twice daily beginning on the day of stem cell reinfusion (24-48 h after completion of high-dose chemotherapy). Most patients were either discharged to an outpatient setting following completion of their chemotherapy or received all of their chemotherapy in an outpatient setting. Febrile neutropenia was treated with empirical antibiotics in an outpatient setting unless it was complicated by hypotension, renal failure, severe mucositis or other problems. The median duration of neutropenia (absolute neutrophil count below 500/mm3) was 7 days. Neutropenic fever occurred in 62% of patients but clinically documented bacterial infection occurred in only 2 (1.5%) patients during their neutropenic period. No bacteremia was noted. Readmission to the hospital following fever or infection occurred in 26% of patients maintained in the outpatient setting. There were no deaths from a bacterial infection in this study although 1 patient (0.7%) died from aspergillosis. Prophylactic ciprofloxacin and rifampin is a well-tolerated and highly effective combination that effectively decreases the risk of both gram-positive and gram-negative bacterial infection following HDC/ASCR. It facilitates outpatient management of myelosuppressed patients receiving autologous stem cell rescue.

Topics: Ambulatory Care; Anti-Infective Agents; Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Ciprofloxacin; Combined Modality Therapy; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Neoplasms; Rifampin; Transplantation, Autologous; Treatment Outcome

The susceptibility of clinical isolates of methicillin-susceptible and -resistant staphylococci from cancer patients with central venous catheter bacteremia to quinupristin/dalfopristin, a semisynthetic streptogramin, was determined in vitro. Susceptibility of these isolates to nine other antistaphylococcal antibiotics was also determined for comparison. A total of 197 staphylococcal strains were tested from 1983 to 1992. Quinupristin/dalfopristin was bactericidal against all isolates, independent of their resistance to methicillin. Its activity was similar to that of vancomycin but superior to that of teicoplanin. Quinupristin/dalfopristin may prove to be an important addition to our armamentarium against catheter-related staphylococcal infections.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Bacteremia; Catheterization, Central Venous; Cefamandole; Cephalosporins; Ciprofloxacin; Clindamycin; Daptomycin; Humans; Methicillin; Methicillin Resistance; Microbial Sensitivity Tests; Neoplasms; Novobiocin; Oxacillin; Penicillins; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Teicoplanin; Vancomycin; Virginiamycin

A total of 440 fresh clinical isolates of yeasts from cancer patients were tested by an agar dilution technique against miconazole, miconazole nitrate, and ketoconazole individually and combined with 5 micrograms of rifampin per ml. Most strains of Candida albicans were susceptible to 0.5 microgram or less of the imidazoles per ml. Candida tropicalis required 2 to 4 micrograms of miconazole and its nitrate base per ml for inhibition and was resistant to ketoconazole. The 100% minimal inhibitory concentration of the imidazoles for Candida krusei was 1 microgram/ml. Susceptibility to 4 micrograms of miconazole and miconazole nitrate per ml occurred in 73 and 87% of Torulopsis glabrata strains, respectively, and none was susceptible to ketoconazole. Miconazole was most effective against the Candida spp., whereas its nitrate base was most active against T. glabrata. Synergy was observed when rifampin was combined with miconazole and miconazole nitrate but was not observed when rifampin was combined with ketoconazole. Synergy occurred most frequently when rifampin was combined with miconazole nitrate.

Topics: Antifungal Agents; Candida; Drug Synergism; Humans; Imidazoles; Ketoconazole; Miconazole; Microbial Sensitivity Tests; Neoplasms; Piperazines; Rifampin

Topics: Agranulocytosis; Blood Bactericidal Activity; Candida; Chediak-Higashi Syndrome; Chromosome Aberrations; Chromosome Disorders; Female; Glucosephosphate Dehydrogenase Deficiency; Glutathione Peroxidase; Granulomatous Disease, Chronic; Heterozygote; Humans; Infant, Newborn; Leukocytes; Lupus Erythematosus, Discoid; Male; Neoplasms; Neutropenia; Neutrophils; Peroxidases; Phagocytosis; Pregnancy; Rifampin; Sulfonamides; Vitamin B 6 Deficiency

Topics: Antineoplastic Agents; Dactinomycin; Doxorubicin; Enzyme Inhibitors; Fluorouracil; Isoenzymes; Methotrexate; Neoplasms; Rifampin

Topics: Cell Division; Cell Line; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Doxorubicin; Drug Evaluation, Preclinical; Female; Fibroblasts; Humans; Melanoma; Neoplasms; Osteosarcoma; Rifampin; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms

Topics: Animals; Antiviral Agents; Avian Leukosis Virus; Cats; Cell Differentiation; Cell Transformation, Neoplastic; Chemical Phenomena; Chemistry; DNA Nucleotidyltransferases; DNA Replication; DNA, Viral; Humans; Leukocytes; Lymphatic System; Neoplasms; Oncogenic Viruses; Retroviridae; Rifampin; RNA Viruses; RNA, Neoplasm; RNA, Viral; Time Factors; Viral Interference

Topics: Antiviral Agents; Brain; Humans; Interferons; Leukoencephalopathy, Progressive Multifocal; Neoplasms; Oncogenic Viruses; Papillomaviridae; Polyomaviridae; Rifampin; Streptovaricin; Virus Diseases

Topics: Culture Techniques; DNA Nucleotidyltransferases; Humans; Neoplasms; Rifampin; RNA

Topics: Antineoplastic Agents; Cytopathogenic Effect, Viral; Enzyme Induction; Feedback; Infections; Lysogeny; Neoplasms; Nucleic Acids; Penicillins; Rickettsia; Rifampin; Tetracycline; Virus Diseases