acyclovir and Kidney-Diseases

A previously healthy 30-year-old woman was admitted to our hospital because of impaired consciousness after convulsion. A temporary diagnosis of herpes simplex encephalitis was made, and intravenous acyclovir (ACV) therapy (250 mg four times daily in normal saline over 2 hours) was started. Three days later, she became confused, and was having hallucinations, dysarthria and generalized painful seizures occurred without focal neurologic deficit. Whether the neuropsychiatric symptoms were related to herpes simplex encephalitis or acyclovir neurotoxity was initially unclear. The brain MRI and lumbar puncture findings were initially normal, but abnormal FLAIR lesions appeared later. ACV-associated encephalopathy was considered. ACV was discontinued, and she recovered from the neurological disorder within 24 hours. Although blood levels of acyclovir were not determined, it is unlikely that they were in a toxic range, in view of her normal renal function.

Topics: Acute Disease; Acyclovir; Adult; Antiviral Agents; Brain Diseases; Dysarthria; Encephalitis, Viral; Epilepsy, Generalized; Female; Hallucinations; Humans; Kidney Diseases; Magnetic Resonance Imaging

Topics: Acyclovir; Anti-Infective Agents; Antiviral Agents; Ciprofloxacin; Humans; Kidney Diseases

Both oral ganciclovir and valacyclovir decrease the incidence of cytomegalovirus (CMV) disease after renal transplantation. Moreover, valacyclovir has been shown to reduce the risk of acute rejection. Our study was designed to compare the efficacy and safety of oral ganciclovir and valacyclovir in the prophylaxis of CMV disease after renal transplantation.. A total of 83 patients were prospectively randomized to 3-month treatment with oral ganciclovir (3 g/day, n=36, GAN) or oral valacyclovir (8 g/day, n=35, VAL). A control group (DEF, n=12) was managed by deferred therapy.. No differences were found in demography, immunosuppression, or donor/recipient CMV serology. The 12-month incidence of CMV disease was 67% in the DEF group compared with 6% in the GAN group and 3% in the VAL group (P<0.001 GAN or VAL vs. DEF; P=0.575 GAN vs. VAL). The biopsy-confirmed acute rejection rate at 12 months was 12% in the VAL group compared with 34% in the GAN group (P=0.030) and 58% in the DEF group (P<0.001). The difference between the GAN and DEF groups was not significant (P=0.087). The average CMV-associated costs per patient were $3,072, $2,906, and $4,906 in the GAN, VAL, and DEF groups, respectively.. Valacyclovir and oral ganciclovir are equally effective in the prevention of CMV disease after renal transplantation. Both regimens are cost-effective. Valacyclovir is associated with a significantly reduced risk of acute rejection compared with both ganciclovir prophylaxis and deferred therapy.

Topics: Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Graft Rejection; Histocompatibility Testing; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Reoperation; Risk Factors; Survival Analysis; Time Factors; Transplantation, Homologous; Valacyclovir; Valine

Oral ganciclovir and valacyclovir reduce the incidence of cytomegalovirus (CMV) disease after renal transplantation (RTx). Our study was designed to compare the efficacy, costs, and safety of oral ganciclovir and valacyclovir in the prophylaxis of CMV disease over the first 6 months after RTx. A total of 38 patients was randomized to 3-month treatment with either oral ganciclovir (1 g t.i.d., n=14, GAN group) or oral valacyclovir (2 g q.i.d., n=12, VAL group). A third group (C, n=12) received no prophylaxis. The patients were monitored by CMV-nested PCR in whole blood. No differences were found between the groups in their demographic characteristics, immunosuppressive protocols, or donor and recipient CMV serology. Thirty-six out of 38 (94.7%) recipients were CMV-seropositive. Over the 6-month post-RTx period, there were 13 episodes of CMV disease in eight (66.7%) patients of the C group compared with none in the GAN and VAL groups ( P=0.0005, GAN vs C; P=0.001, VAL vs C). The incidence of CMV viremia was 30.8%, 50.0%, and 91.7% in the GAN, VAL, and C groups, respectively ( P=0.004, GAN vs C; P=0.07, VAL vs C; P=NS, GAN vs VAL). Treatment failure (death, graft loss, CMV disease, or withdrawal from study) occurred in 14.3%, 0% and 66.7% in the GAN, VAL, and C groups, respectively ( P=0.014, GAN vs C; P=0.001, VAL vs C; P=NS, GAN vs VAL). The average CMV-associated costs per patient (in 2001 euros) were 2,449+/-1,178, 2,485+/-581, and 4,259+/-4,616 in the GAN, VAL, and C groups, respectively. Ganciclovir and valacyclovir were well tolerated, with ganciclovir having had to be withdrawn shortly in one patient only because of thrombocytopenia. In conclusion, oral ganciclovir and valacyclovir are equally safe and effective in the prophylaxis of CMV disease after RTx. Both are cost-effective and help reduce CMV-associated costs by some 40% compared with patients without prophylaxis.

Topics: Acyclovir; Administration, Oral; Adult; Antiviral Agents; Cadaver; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Female; Ganciclovir; Humans; Kidney Diseases; Kidney Transplantation; Living Donors; Male; Middle Aged; Postoperative Complications; Prospective Studies; Renal Insufficiency; Tissue Donors; Valacyclovir; Valine

Varicella, or chickenpox, is very communicable and has been shown to be transmitted to nearly 90% of household contacts. Severe varicella infections with fatal complications have been noted in children receiving corticosteroids despite the administration of varicella-zoster immune globulin (VZIG). The use of post-exposure acyclovir prophylaxis in immunocompetent children exposed to a household contact with varicella has been shown to decrease the transmission rate of varicella significantly. We studied the safety and efficacy of acyclovir prophylaxis as an adjunctive preventive measure in 8 children (10 separate exposures) receiving corticosteroids for renal disease. Four children (6 separate exposures) served as controls. No adverse reactions were reported with the acyclovir prophylaxis. The maximum change between pre- and study serum creatinine levels was 0.1 mg/dl. None of the 8 patients who received acyclovir prophylaxis developed chickenpox. One of these 8 patients developed humoral immunity to varicella despite the absence of clinical infection. One of 4 patients who received VZIG prophylaxis alone developed chickenpox. These data support the use of acyclovir prophylaxis as an adjunctive measure to VZIG for the prevention of potentially serious varicella infection in children receiving steroids.

Topics: Acyclovir; Adolescent; Adrenal Cortex Hormones; Antiviral Agents; Chickenpox; Child; Child, Preschool; Female; Graft Rejection; Humans; Kidney Diseases; Kidney Transplantation; Male; Nephrotic Syndrome

Topics: Acyclovir; Adolescent; Chickenpox; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Immunocompetence; Infusions, Parenteral; Kidney Diseases; Male; Time Factors

Six patients with hepatitis B virus (HBV) related chronic liver disease were treated with acyclovir, 5-15 mg/kg 8 hourly, given as an iv bolus or iv infusion over 1 h for up to 7 days. Two patients treated with 10 and 15 mg/kg 8 hourly showed a decrease in HBV-DNA polymerase and HBV-DNA when mean trough acyclovir plasma concentrations of 5.0 +/- 0.6 and 13.2 +/- 3.0 microM were attained. Inhibition of viral replication was not seen in patients treated with lower doses. Transient renal impairment was seen in two patients who received high dosage by the iv bolus mode of administration. This complication may be prevented by a high oral fluid intake or iv infusion of the drug over 1 h. Further study with acyclovir 15 mg/kg 8-hourly given as an iv infusion for longer periods is warranted.

Topics: Acyclovir; Adolescent; Adult; Chronic Disease; DNA, Viral; Hepatitis B; Humans; Injections, Intravenous; Kidney Diseases; Time Factors; Virus Replication

Acyclovir (ACV) is a nucleoside antivirus-free agent that was developed and marketed by Burroughs Well-come of the United States. Renal damage from ACV has been a major factor limiting its clinical application. Thus, the renal toxicity mechanism of ACV requires systematic study. In our previous study, we speculated that the nephrotoxicity of ACV may be associated with oxidative stress. In addition to the study of ACV's toxic effect

Topics: Acyclovir; Animals; Antiviral Agents; Chromatography, High Pressure Liquid; Drug Administration Schedule; Injections, Intravenous; Kidney; Kidney Diseases; Microdialysis; Models, Biological; Rats, Sprague-Dawley; Toxicokinetics

To assess the incidence, predictive factors, and prognosis of acyclovir-induced nephrotoxicity. We conducted a historical prospective cohort study of patients treated with intravenous acyclovir in North Denmark Region from 2009 to 2016. Information on baseline demographics, co-morbidities, plasma creatinine, and treatment was obtained from the medical records. The primary outcome was an increase of ≥ 40 μmol/L in plasma creatinine level from baseline. We included 276 patients treated with intravenous acyclovir of which 29 (10.5%) met the primary outcome. In 14 cases, the treating physician considered acyclovir the main reason for nephrotoxicity, whereas a potential competing cause of renal impairment was present among the 15 remaining patients. Hypertension was the only predictive factor associated with nephrotoxicity (risk ratio (RR), 2.77; 95% confidence interval (CI), 1.41-5.46), while having no co-morbidities was protective (RR, 0.32; CI, 0.16-0.63). In all cases, the nephrotoxicity was reversible following rehydration and dose reduction or discontinuation of the drug. However, the normalized plasma creatinine upon treatment was significantly higher between cases with acyclovir-induced nephrotoxicity than cases with a potential competing cause (median [interquartile range (IQR)], 93.5 μmol/L [85-108] vs 75 μmol/L [66.5-88]; p = 0.019). Acyclovir-induced, reversible nephrotoxicity was observed in 5.1-10.5% of patients. It is difficult to predict who will develop acyclovir-induced nephrotoxicity; it may occur late in treatment and hypertension was the only independent predictive factor, while the absence of co-morbidities was protective. Ensuring hydration, frequent evaluations of renal function, and corresponding dose adjustment of intravenous acyclovir treatment seem prudent.

Topics: Acute Kidney Injury; Acyclovir; Administration, Intravenous; Adult; Aged; Antiviral Agents; Cohort Studies; Creatinine; Denmark; Female; Humans; Hypertension; Incidence; Kidney Diseases; Male; Middle Aged; Prognosis; Prospective Studies; Risk Factors

Cytomegalovirus (CMV) is the most common viral infection during the post-transplant period, and it is one of the major causes of morbidity and mortality in kidney transplantation. In this study, the incidence and impact of pre-emptive and prophylactic approaches and long-term effects on graft and patient survival of CMV infection were investigated. Among 493 adult kidney transplant recipients, pretransplant CMV IgG-negative patients and patients with a follow-up shorter than a month were excluded. The patients were divided into 2 groups: pre-emptive group (n = 187, regular screening and acyclovir 400 mg twice daily for 6 months), and prophylaxis group (n = 275, valganciclovir 450 mg/d for 3 months). The pre-emptive group was screened for CMV with either pp65 antigenemia or CMV DNA. There were 462 patients, and mean follow-up was 37.7 months. There were more CMV infections in the pre-emptive group than in the prophylaxis group (n = 56, 30.1% vs n = 12, 4.4%, respectively; P < .001). Late CMV infections were significantly more frequent in the prophylaxis group (10 of 12, 83.3%) than in the pre-emptive group (8 of 56, 14.3%, P < .001). In multivariate analysis, valganciclovir prophylaxis was associated with a lower CMV infection (relative risk [RR]: 0.18, 95% confidence interval [CI] 0.08 to 0.39, P < .001). Delayed graft function was the only independent risk factor for graft loss during the follow-up on multivariate Cox regression analysis (RR: 2.66, 95% GA 1.17 to 6.04, P = .02). Valganciclovir prophylaxis was more protective against CMV infection than the pre-emptive approach. Neither prophylaxis/pre-emptive approaches nor CMV infection had negative effect on graft and patient survival.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Graft Survival; Humans; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Premedication; Risk Factors; Transplant Recipients; Valganciclovir; Young Adult

Apigenin is a flavonoid compound, widely distributed in natural plants. Various studies have suggested that apigenin has inhibitory effects towards several drug transporters, such as the organic anion transporting (OAT) polypeptides, 1B1 and 1B3 (OATP1B1 and OATP1B3). However, the mechanism by which apigenin interacts with OAT1 has not been well studied.. MDCK cells stably-expressing OAT1 were used to examine the inhibitory effects of apigenin on OAT1. UPLC-MS/MS was used to evaluate the in vitro and in vivo effects of apigenin on the uptake of acyclovir by OAT1. Cytotoxicity was determined by the cell viability, MTT assays.. Apigenin effectively inhibited the activity of OAT1 in a dose-dependent manner with an IC50 value of 0.737μM. Pre-incubation of cells with apigenin caused a time-dependent inhibition (TDI) of OAT1. Additionally, we examined the interactions between apigenin and acyclovir or adefovir. Data showed that apigenin (1μM) significantly blocked the uptake of acyclovir by OAT1 in vitro with an inhibition rate of 55%. In vivo, apigenin could increase the concentration of acyclovir in plasma when co-administered with acyclovir. Importantly, the MTT assays showed that, at a dose of 50μM, apigenin significantly reduced the cytotoxicity of adefovir and substantially increased cell viability from 50.6% to 112.62%.. Our results demonstrate that apigenin regulates OAT1, and can cause TDI or herb-drug interaction (HDI) when used in combination with acyclovir or adefovir. Therefore, apigenin could be used as a nephroprotective agent when used in combination with the substrates of OAT1.

Topics: Acyclovir; Adenine; Animals; Antiviral Agents; Apigenin; Cell Survival; Chromatography, High Pressure Liquid; Dogs; Dose-Response Relationship, Drug; Herb-Drug Interactions; Inhibitory Concentration 50; Kidney Diseases; Madin Darby Canine Kidney Cells; Male; Organic Anion Transport Protein 1; Organophosphonates; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Time Factors

Topics: Acyclovir; Adult; Antiviral Agents; Chickenpox; Female; Humans; Kidney Diseases; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious

Topics: Acyclovir; Adult; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antiviral Agents; Creatinine; Female; Humans; Kidney Diseases; Magnetic Resonance Imaging; Multiple Sclerosis, Relapsing-Remitting

The occurrence of nephrotoxicity with vancomycin is approximately 17%, but can increase to 35% when combined with other nephrotoxic agents. Patients with hematologic malignancies may be at greater risk for vancomycin-induced nephrotoxicity due to nephrotoxic chemotherapy and tumor lysis syndrome.. The primary objective of this study was to determine the occurrence of nephrotoxicity in adult patients with leukemia receiving vancomycin.. A retrospective review approved by the Institutional Review Board was conducted on adult patients with leukemia who received at least one dose of vancomycin during hospital admission between 1 January 2009 and 30 April 2009.. Forty patients had an occurrence of nephrotoxicity (16%) while 210 patients did not have an occurrence of nephrotoxicity. In multivariate analysis, variables significantly associated with development of nephrotoxicity included active disease status (odds ratio, 4.38 [95% CI 1.1-29.4], p = 0.0291), concomitant intravenous acyclovir administration (odds ratio, 3.83 [95% CI, 1.6-8.9]; p = 0.0022), and concomitant amphotericin administration (odds ratio, 4.26 [95% CI, 1.9-9.4]; p = 0.0004).. The occurrence of nephrotoxicity in patients with leukemia treated with vancomycin was 16% in our study, similar to previously published reports. Active disease status and concomitant use of intravenous acyclovir and amphotericin were identified as significant risk factors for development of nephrotoxicity. The presence of risk factors for vancomycin nephrotoxicity should be evaluated prior to initiation of therapy to determine appropriateness of use.

Topics: Acyclovir; Administration, Intravenous; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Female; Humans; Kidney Diseases; Leukemia; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Risk Factors; Vancomycin

Acyclovir (ACV) is an antiviral agent. However, its use is limited by adverse side effect, particularly by its nephrotoxicity. Metabonomics technology can provide essential information on the metabolic profiles of biofluids and organs upon drug administration. Therefore, in this study, mass spectrometry-based metabonomics coupled with multivariate data analysis was used to identify the plasma metabolites and metabolic pathways related to nephrotoxicity caused by intraperitoneal injection of low (50mg/kg) and high (100mg/kg) doses of acyclovir. Sixteen biomarkers were identified by metabonomics and nephrotoxicity results revealed the dose-dependent effect of acyclovir on kidney tissues. The present study showed that the top four metabolic pathways interrupted by acyclovir included the metabolisms of arachidonic acid, tryptophan, arginine and proline, and glycerophospholipid. This research proves the established metabonomic approach can provide information on changes in metabolites and metabolic pathways, which can be applied to in-depth research on the mechanism of acyclovir-induced kidney injury.

Topics: Acyclovir; Animals; Antiviral Agents; Biomarkers; Dose-Response Relationship, Drug; Kidney; Kidney Diseases; Male; Mass Spectrometry; Metabolic Networks and Pathways; Metabolomics; Multivariate Analysis; Plasma; Rats

Acyclovir (ACV) is an effective and widely used antiviral agent. However, its clinical application is limited by severe nephrotoxicity. We assessed ACV-induced nephrotoxicity and identified the differentially expressed proteins using mass spectrometry-based proteomic analysis. In total, 30 ICR mice were intraperitoneally administrated ACV (150 or 600 mg/kg per day) for 9 days. After administration of ACV, levels of serum creatinine and urea nitrogen increased significantly. In addition, mouse kidneys exhibited histopathological changes and reduced expression levels of vascular endothelial growth factor (VEGF) and its receptor VEGFR2. In the proteomic analysis, more than 1,000 proteins were separated by two-dimensional polyacrylamide gel electrophoresis, and a total of 20 proteins were up- or down-regulated in the ACV group compared with the saline group. Among these, six proteins (MHC class II antigen, glyoxalase 1, peroxiredoxin 1, αB-crystallin, fibroblast growth factor receptor 1-IIIb, and cytochrome c oxidase subunit Vb) were identified in association with ACV-induced nephrotoxicity. These findings were confirmed by Western blotting analysis. The differential expression levels of α-BC, Prx1, Glo I and CcO Vb suggest that oxidative damage and mitochondrial injury may be involved in ACV-induced nephrotoxicity. Furthermore, VEGF and FGF may play a role in tissue repair and the restoration process following ACV nephrotoxicity.

Topics: Acyclovir; Animals; Antiviral Agents; Creatinine; Disease Models, Animal; Kidney; Kidney Diseases; Kidney Function Tests; Mice; Mice, Inbred ICR; Proteome; Proteomics; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

Valacyclovir, the L-valyl ester prodrug of acyclovir (ACV), is widely prescribed to treat infections caused by varicella-zoster virus or herpes simplex virus. Rarely, treatment is complicated by reversible neuropsychiatric symptoms. By mechanisms not fully understood, this occurs more frequently in the setting of renal impairment. We characterized the steady-state pharmacokinetics of ACV and its metabolites 9-[(carboxymethoxy)methyl]guanine (CMMG) and 8-hydroxy-acyclovir (8-OH-ACV) in cerebrospinal fluid (CSF) and the systemic circulation. We administered multiple doses of high-dose valacyclovir to 6 subjects with normal renal function and 3 subjects with chronic renal impairment (creatinine clearance [CrCl], approximately 15 to 30 ml/min). Dosages were 2,000 mg every 6 h and 1,500 mg every 12 h, respectively. Indwelling intrathecal catheters allowed serial CSF sampling throughout the dosing interval. The average steady-state concentrations of acyclovir, CMMG, and 8-OH-ACV were greater in both the systemic circulation and the CSF among subjects with impaired renal function than among subjects with normal renal function. However, the CSF penetration of each analyte, reflected by the CSF-to-plasma area under the concentration-time curve over the 6- or 12-h dosing interval (AUC(tau)) ratio, did not differ based on renal function. Renal impairment does not alter the propensity for ACV or its metabolites to distribute to the CSF, but the higher concentrations in the systemic circulation, as a result of reduced elimination, are associated with proportionally higher concentrations in CSF.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Chronic Disease; Female; Guanine; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Male; Medical Futility; Middle Aged; Prodrugs; Valacyclovir; Valine; Young Adult

The study aimed to predict effective human jejunal permeability (P(eff)) using a biophysical model based on parametrized paracellular, aqueous boundary layer, and transcellular permeabilities, and the villus-fold surface area expansion factor (k(VF)). Published human jejunal data (119 P(eff), 53 compounds) were analyzed by a regression procedure incorporating a dual-pore size paracellular model. Transcellular permeability, scaled by k(VF), was equated to that of Caco-2 at pH 6.5. The biophysical model predicted human jejunal permeability data within the experimental uncertainty. This investigation revealed several surprising predictions: (i) many molecules permeate predominantly (but not exclusively) by the paracellular route, (ii) the aqueous boundary layer thickness in the intestinal perfusion experiments is larger than expected, (iii) the mucosal surface area in awake humans is apparently nearly entirely accessible to drug absorption, and (iv) the relative "leakiness" of the human jejunum is not so different from that observed in a number of published Caco-2 studies.

Topics: Animals; Disease Models, Animal; Dogs; Humans; Jejunal Diseases; Kidney Diseases; Models, Biological; Permeability; Porosity; Regression Analysis

Topics: Acyclovir; Aged; Aged, 80 and over; Antiviral Agents; Contraindications; Dose-Response Relationship, Drug; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Renal Dialysis; Valacyclovir; Valine

Acyclovir-induced nephrotoxicity is well known, but published literature lacks information on the safety of substitution with other antiviral agents. We describe four patients with acyclovir-induced renal toxicity that were subsequently managed with hydration and famciclovir. All four patients subsequently had improvements in their symptoms with full recovery of their baseline renal function.

Topics: 2-Aminopurine; Acyclovir; Aged; Aged, 80 and over; Antiviral Agents; Famciclovir; Female; Herpes Simplex; Herpes Zoster; Humans; Kidney Diseases; Male; Middle Aged

Management of meningo-encephalitis often involves the need for antibiotic and antiviral treatment. We report a retrospective analysis over a 6-month period of 17 patients (age range 1-14 years) who were treated with combination therapy of ceftriaxone and acyclovir. Mean acyclovir and ceftriaxone doses were 1,222+/-304 and 2,315+/-509 mg/m(2) per day, respectively. Three patients developed acute renal failure with a peak creatinine of up to 865% above baseline, occurring 2-3 days after starting combination therapy. Patients revealed a tubular proteinuria pattern. Renal biopsy of 1 patient showed a tubulotoxic picture but no evidence of crystals. In 12 of 17 patients (70%) there was a significant increase in serum creatinine. This was significantly greater than literature reports of 16% with acyclovir monotherapy. The degree of renal impairment in our patients correlated significantly with the acyclovir dose, while no correlation was found with the ceftriaxone dose. We conclude that the addition of a second nephrotoxic drug aggravated the extent of renal injury in our patients. The mechanism is tubulotoxicity. Caution should be exercised when using this potentially nephrotoxic cocktail, with clear criteria established for the initiation of combination therapy and close monitoring of serum creatinine.

Topics: Acyclovir; Adolescent; Antiviral Agents; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Creatinine; Drug Combinations; Female; Humans; Infant; Kidney; Kidney Diseases; Kidney Function Tests; Male; Retrospective Studies

The antiviral effect of azidothymidine (AZT) can be potentiated by acyclovir (ACV), and this drug association has been used in the management of HIV-infected patients. In the present study we examined the effects of this association on the livers and kidneys of both pregnant rats and their concepts. Previous data from this laboratory suggested that the deleterious effects of ACV on rat pregnancy are due to its extraplacental actions and these are, at least in part, counteracted by concomitant treatment with AZT. Kidneys and livers of pregnant rats were noticed to be much more sensitive to the toxic action of the drugs than those of their concepts, ACV eliciting much more evident morphological alterations than did AZT. Contrary to what was expected, in the group of rats treated with both drugs AZT was not able to diminish the severity of the alterations evoked by ACV. The proposed "protective" action of AZT against the abortive effect of ACV on rat pregnancy does not seem to be exerted through a renal or hepatic pathway.

Topics: Abortion, Spontaneous; Acyclovir; Animals; Antiviral Agents; Chemical and Drug Induced Liver Injury; Drug Synergism; Female; Kidney; Kidney Diseases; Liver; Liver Diseases; Pregnancy; Pregnancy Complications; Rats; Rats, Wistar; Zidovudine

A reversed-phase ion-pair high-performance liquid chromatography method for the determination of acyclovir and its metabolite 9-carboxymethoxymethylguanine is described. The sample are purified by reversed-phase solid-phase extraction. The components are separated on a C18 column with a mobile phase containing 18% acetonitrile, 5 mM dodecyl sulphate and 30 mM phosphate buffer, pH 2.1, and measured by fluorescence detection using an excitation wavelength of 285 nm and an emission wavelength of 380 nm. Detection limits are 0.12 microM (plasma) and 0.60 microM (urine) for acyclovir, and 0.26 microM (plasma) and 1.3 microM (urine) for metabolite. Correlation coefficients that were better than 0.998 were obtained normally. This analytical method, which enables simultaneous measurement of parent compound and metabolite, has been used in kinetics studies and for therapeutic drug monitoring in different patient groups with variable degrees of renal dysfunction.

Topics: Acyclovir; Antiviral Agents; Chromatography, High Pressure Liquid; Guanine; Humans; Kidney Diseases; Kidney Transplantation

Topics: 2-Aminopurine; Abnormalities, Drug-Induced; Acyclovir; Amantadine; Antiviral Agents; Cidofovir; Contraindications; Cytosine; Drug Resistance, Microbial; Eye Infections, Viral; Famciclovir; Foscarnet; Ganciclovir; Guanine; Humans; Interferon-alpha; Kidney Diseases; Lamivudine; Organophosphonates; Organophosphorus Compounds; Prodrugs; Ribavirin; Rimantadine; Trifluridine; Valacyclovir; Valine; Virus Diseases

Topics: Acyclovir; Aged; Brain Diseases; Female; Humans; Kidney Diseases; Renal Insufficiency

Topics: Acyclovir; Animals; Blood Urea Nitrogen; Body Weight; Glycosuria; Kidney Diseases; Male; Micropore Filters; Microvilli; Phosphates; Polyuria; Rats; Rats, Wistar; Time Factors

To determine the pharmacokinetic parameters of acyclovir disposition in neonates with renal dysfunction.. Prospective sequential open enrollment of neonates with presumed herpes group virus infections.. Neonatal intensive care units in the greater Minneapolis-St. Paul metropolitan area.. Sixteen neonates with gestational ages between 27 and 40 weeks (median 38 weeks) were given acyclovir between days 1 and 56 of life to treat presumed herpes virus infections. Six infants were critically ill with multisystem disease, five infants had hepatic failure and underwent blood exchange transfusion, and five infants had renal failure. A mean of four (range 1 to 19) serum acyclovir concentrations per patient were measured by radioimmunoassay. Pharmacokinetic parameters were calculated from acyclovir concentrations in 46 samples from 16 patients.. The pharmacokinetic disposition of acyclovir was described as a two-compartment model. Although the ranges for acyclovir clearance and terminal elimination (t 1/2 beta) were wide, a statistically significant relationship was demonstrated between clearance and beta versus serum creatinine concentration. The average t 1/2 beta for infants with serum creatinine level less than 1 mg/dl (88 mumol/L) was 5.0 hours, and 15.6 hours for those with serum creatinine level greater than 1 mg/dl.. Neonates with hepatic or renal dysfunction or young premature infants accumulate acyclovir when dosed without adjustment for organ dysfunction. Measurement of serum creatinine or creatinine clearance can be useful in the dosing of acyclovir in neonates.

Topics: Acyclovir; Creatinine; Herpes Simplex; Herpes Zoster; Humans; Infant; Infant, Newborn; Infant, Premature; Kidney Diseases; Liver Diseases; Prospective Studies

We assessed the effect of acyclovir therapy on renal function during a course of therapy for herpesvirus disease. Renal function was assessed by measuring the clearances of inulin, albumin, and beta 2-microglobulin at the beginning and end of acyclovir therapy. Thirty-two patients had valid paired inulin clearances and 21 had valid paired albumin and beta 2-microglobulin clearances. No significant mean decrement of renal function was observed; however, 2 patients had a reversible renal dysfunction associated with acyclovir therapy which disappeared soon after discontinuation of the drug and was unassociated with a prior or recurrent renal dysfunction in short-term follow-up.

Topics: Acyclovir; Aged; Albuminuria; beta 2-Microglobulin; Child; Creatinine; Female; Herpesviridae Infections; Humans; Immunosuppression Therapy; Infusions, Intravenous; Inulin; Kidney Diseases; Kidney Transplantation; Male

Limited information is available concerning the use of ganciclovir (GCV) in patients with severe renal impairment. The pharmacokinetics of GCV were studied in a heart transplant recipient requiring hemodialysis. The total body clearance was calculated to be approximately 5% of that previously reported for patients with normal renal function. GCV was removed by hemodialysis; a single 4-h procedure decreased the concentration in plasma by approximately 50%. GCV can be safely administered to patients with renal insufficiency if concentrations in plasma are monitored.

Topics: Acyclovir; Adult; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Kidney Diseases; Renal Dialysis

Topics: Acyclovir; Humans; Kidney Diseases; Male; Mental Disorders; Middle Aged

Ten marrow transplant recipients with biopsy-proven cytomegalovirus pneumonia were treated with the acyclic nucleoside analog 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine (BW B759U). Viruria and viremia ceased after 4 days of treatment in all patients with cultures initially positive from these sites. Cytomegalovirus was eliminated from respiratory secretions after a median of 8 days. Despite this antiviral effect, only one patient survived the pneumonia. Quantitative cultures of lung tissue before and after treatment confirmed that therapy with BW B759U was associated with substantial antiviral activity, with a mean decrease in viral titers of more than 99.99% after treatment. Neutropenia developed in three patients when mean peak and trough plasma levels exceeded 50 and 10 mu mol/L, respectively, but no other toxicity was seen. BW B759U is the first antiviral agent showing consistent activity against cytomegalovirus in vivo, and it should be evaluated in the earlier management of cytomegalovirus infections after marrow transplantation and in serious cytomegalovirus infections in other immunocompromised patients.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Bone Marrow Transplantation; Child, Preschool; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Kidney Diseases; Lung; Male; Neutropenia; Pneumonia, Viral; Postoperative Complications; Tissue Distribution

Topics: Acyclovir; Drug Interactions; Humans; Kidney Diseases; Male; Meperidine; Middle Aged; Nervous System Diseases

A case of fulminant hepatic failure, associated with infectious mononucleosis, in a previously healthy 14-year-old girl is reported. Despite intensive therapy, which included the use of acyclovir, charcoal haemoperfusion, and measures to control her raised intracranial pressure (guided by serial EEG and auditory brainstem-evoked response recordings), the outcome was fatal.

Topics: Acyclovir; Adolescent; Brain Diseases; Charcoal; Female; Hemoperfusion; Humans; Infectious Mononucleosis; Kidney Diseases

Thirteen recipients of bone marrow transplants were given high-dose acyclovir and alpha-interferon (Cantell interferon) for the treatment of biopsy-proven cytomegaloviral pneumonia. Three patients survived. Doses of acyclovir between 500 and 1,000 mg/m2 of body surface area (peak plasma levels, 7-86 micrograms/ml) and doses of interferon between 2 X 10(4) and 40 X 10(4) units/kg per day (peak serum levels, 5-608 units/ml) were given. No consistent antiviral effect was seen despite the large doses employed. Possible marrow toxicity associated with this regimen occurred in five patients, neurologic symptoms in two, and nephrotoxicity in one. Thus, treatment with high-dose acyclovir plus alpha-interferon was moderately toxic but ineffective against cytomegaloviral pneumonia after bone marrow transplantation.

Topics: Acyclovir; Bone Marrow Transplantation; Combined Modality Therapy; Cytomegalovirus Infections; Humans; Interferon Type I; Kidney Diseases; Nervous System Diseases; Pneumonia, Viral