rifampin and Lymphoma--Non-Hodgkin

Bortezomib, an antineoplastic agent with proteasome inhibitory activity, is extensively metabolized by the hepatic microsomal cytochrome P450 (CYP) enzymes CYP3A4 and CYP2C19. Drugs that affect these enzymes may therefore have an impact on the pharmacological profile of bortezomib. This study evaluated the effects of co-administration of a potent CYP3A4 inducer (rifampicin [rifampin]) and a weak CYP3A4 inducer (dexamethasone) on the pharmacokinetic, pharmacodynamic and safety profiles of bortezomib.. Patients aged ≥18 years with relapsed or refractory multiple myeloma or non-Hodgkin's lymphoma received intravenous bortezomib 1.3 mg/m2, administered on days 1, 4, 8 and 11 of a 21-day cycle, for 3 cycles. In stage 1, patients were randomized (1 : 1) to receive bortezomib alone or in combination with oral rifampicin 600 mg once daily on days 4-10 during cycle 3 only. If the mean area under the plasma concentration-time curve (AUC) of bortezomib was reduced by ≥30% during rifampicin co-administration, then stage 2 was initiated, in which patients received bortezomib with dexamethasone 40 mg once daily on days 1-4 and days 9-12 during cycle 3 only. Blood samples were collected on days 11 through 14 of cycles 2 and 3 before and after bortezomib administration, at prespecified time points, for pharmacokinetic and pharmacodynamic (proteasome inhibition) assessments.. Twelve patients in the bortezomib-alone arm, six patients in the bortezomib plus rifampicin arm and seven patients in the bortezomib plus dexamethasone arm were included in the pharmacokinetics-evaluable set. Rifampicin reduced the mean AUC from 0 to 72 hours (AUC(72h)) of bortezomib by approximately 45% (223 ng · h/mL in cycle 2 vs 123 ng · h/mL in cycle 3), while dexamethasone had no effect (mean AUC(72h): 179 ng · h/mL in cycle 2 vs 170 ng · h/mL in cycle 3). Proteasome inhibition parameters in peripheral blood were unaffected by rifampicin or dexamethasone. Safety profiles were similar across the treatment arms and consistent with previous experience of bortezomib.. In patients with multiple myeloma or non-Hodgkin's lymphoma, co-administration of rifampicin decreased the exposure to bortezomib but did not affect the proteasome inhibition or safety profiles; co-administration of dexamethasone did not affect the exposure to bortezomib, proteasome inhibition or safety profiles. Concomitant administration of bortezomib with strong CYP3A4 inducers such as rifampicin is not recommended, as it may result in a reduction of the clinical effect, whereas concomitant administration of weak CYP3A4 inducers such as dexamethasone does not affect the pharmacological profile of bortezomib.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Area Under Curve; Boronic Acids; Bortezomib; Cytochrome P-450 CYP3A; Dexamethasone; Drug Combinations; Enzyme Induction; Female; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Multiple Myeloma; Protease Inhibitors; Pyrazines; Rifampin

The DNA alkylating prodrug cyclophosphamide (CPA), alone or in combination with other agents, is one of the most commonly used anti-cancer agents. As a prodrug, CPA is activated by cytochrome P450 2B6 (CYP2B6), which is transcriptionally regulated by the human constitutive androstane receptor (hCAR). Therefore, hCAR agonists represent novel sensitizers for CPA-based therapies. Among known hCAR agonists, compound 6-(4-chlorophenyl)imidazo-[2,1-b]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime (CITCO) is the most potent and broadly utilized in biological studies. Through structural modification of CITCO, we have developed a novel compound DL5016 (32), which has an EC

Topics: Antineoplastic Agents; Cell Proliferation; Cell Survival; Constitutive Androstane Receptor; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Hep G2 Cells; Humans; Lymphoma, Non-Hodgkin; Molecular Structure; Prodrugs; Receptors, Cytoplasmic and Nuclear; Structure-Activity Relationship; Tumor Cells, Cultured

Tuberculosis (TB) is the most common cause of cervical lymphadenopathy in the TB-endemic zone, like India but it can also mimic other diseases. Four cases of cervical lymphadenopathy presented to us as initial treatment failure after completion of six months of antitubercular drugs (ATD), including rifampicin, isoniazid, pyrazinamide, and ethambutol. All were diagnosed as having tuberculosis either by fine needle aspiration cytology or clinically from outside our institution. In one case, tuberculosis was the final diagnosis but, unfortunately, it was multidrug-resistant. In other three cases, Hodgkin disease, Non-Hodgkin lymphoma, and Kikuchi's disease were the diagnoses. In resource-poor countries, like India, which is also a TB-endemic zone, TB should be the first diagnosis in all cases of chronic cervical lymphadenopathy, based on clinical and/or cytological evidences. So, they were correctly advised antitubercular therapy (ATT) initially. Sometimes, TB mimics other aetiologies where apparent initial improvement with ATT finally results in treatment failure. Hence, investigations for microbiological and histopathological diagnosis are warranted, depending on the resources and feasibility. If these tests are not routinely available, the patients should be under close monitoring so that lymphoma, drug-resistant TB, or other aetiologies of cervical lymphadenopathy are not missed. Patients with cervical lymphadenopathy rarely presents acutely; so, a physician can take the opportunity of histopathological study of lymphnode tissue.

Topics: Adolescent; Adult; Antitubercular Agents; Biopsy; Diagnostic Errors; Ethambutol; Female; Histiocytic Necrotizing Lymphadenitis; Hodgkin Disease; Humans; India; Isoniazid; Lymphoma, Non-Hodgkin; Male; Middle Aged; Pyrazinamide; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant; Young Adult

After primary infection, some bacteria can remain in a latent state for several years before a new bacteremia, often due to a weakened immune status. This is common for Mycobacterium tuberculosis, less for other pathogens more difficult to have in mind when facing patients with fever. We report the case of an 84-year-old female patient presenting with fever in the months following antilymphoma chemotherapy, due to bacteremic brucellosis (with a hemophagocytic syndrome) probably latent after primary infection as a child.

Topics: Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Brucella melitensis; Brucellosis; Combined Modality Therapy; Cyclophosphamide; Doxycycline; Drug Therapy, Combination; Female; France; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Lymphoma, Non-Hodgkin; Recurrence; Rifampin; Rituximab; Spain; Time Factors; Vidarabine

A 74-year-old man was admitted to the hospital because of chemotherapy for relapsed non-Hodgkin's lymphoma (NHL). The patient became febrile and experienced diarrhea after chemotherapy. Although ceftazidime and amikacin sulfate were administered as empiric therapy, diarrhea was continued. After several days, stool cytotoxin assay for clostridium difficile (C. difficile) was positive and he was diagnosed as having antibiotics-associated colitis (AAC). Although antibiotics were discontinued and both oral vancomycin and metronidazole were administrated, disease was not improved. To rule out the presence of an additional cause of diarrhea, colon fibroscopic examination was performed. It revealed multiple deep ulcerative lesions at right side colon, surface erosive and minute erosive lesions in all continuous colon. Pseudomembranes were not seen. These findings are compatible with AAC without pseudomembranes. There are no reports that the rifampin is effective on refractory AAC. However, we administered oral rifampin for the current patient. The reasons are 1) conventional antibiotics were not effective, 2) rifampin has excellent in vitro activity against C. difficile, and 3) the efficacy of rifampin on relapsing colitis due to C. difficile is established. After administration of rifampin, fever alleviated and diarrhea was improved. Because AAC may result in significant mortality, patients with refractory or fulminant AAC should be treated with oral rifampin from outset.

Topics: Administration, Oral; Aged; Antibiotics, Antitubercular; Clostridioides difficile; Enterocolitis; Humans; Lymphoma, Non-Hodgkin; Male; Rifampin; Severity of Illness Index

A patient with indolent, non-Hodgkin's lymphoma developed a pretibial soft tissue abscess caused by a fastidious mycobacterium. Because the organism could not be definitively identified by standard microbiologic testing, whole cell fatty acid analysis and 16S rDNA sequencing were performed. These procedures identified the organism as Mycobacterium haemophilum. We review the diagnostic considerations with regard to this pathogen.

Topics: Abscess; Aged; Ciprofloxacin; DNA, Bacterial; DNA, Ribosomal; Drug Therapy, Combination; Fatty Acids; Humans; Lymphoma, Non-Hodgkin; Male; Mycobacterium haemophilum; Mycobacterium Infections; Rifampin

Topics: Aged; Diagnosis, Differential; Ethambutol; Female; Humans; Lymphoma, Non-Hodgkin; Mycobacterium; Mycobacterium Infections; Rifampin; Skin Diseases, Infectious

Topics: Animals; Carbon Isotopes; Cattle; Dactinomycin; DNA; Escherichia coli; Filtration; Lymphoid Tissue; Lymphoma, Non-Hodgkin; Methods; Phosphorus Isotopes; Potassium Chloride; Quaternary Ammonium Compounds; Rifampin; RNA; RNA Nucleotidyltransferases; Sulfates; Templates, Genetic; Thymus Gland; Tritium