acyclovir and Body-Weight

A multicenter, open-label study evaluated the single-dose pharmacokinetics and safety of a pediatric oral famciclovir (prodrug of penciclovir) formulation in infants aged 1 to 12 months with suspicion or evidence of herpes simplex virus infection. Individualized single doses of famciclovir based on the infant's body weight ranged from 25 to 175 mg. Eighteen infants were enrolled (1 to <3 months old [n = 8], 3 to <6 months old [n = 5], and 6 to 12 months old [n = 5]). Seventeen infants were included in the pharmacokinetic analysis; one infant experienced immediate emesis and was excluded. Mean C(max) and AUC(0-6) values of penciclovir in infants <6 months of age were approximately 3- to 4-fold lower than those in the 6- to 12-month age group. Specifically, mean AUC(0-6) was 2.2 microg h/ml in infants aged 1 to <3 months, 3.2 microg h/ml in infants aged 3 to <6 months, and 8.8 microg h/ml in infants aged 6 to 12 months. These data suggested that the dose administered to infants <6 months was less than optimal. Eight (44.4%) infants experienced at least one adverse event with gastrointestinal events reported most commonly. An updated pharmacokinetic analysis was conducted, which incorporated the data in infants from the present study and previously published data on children 1 to 12 years of age. An eight-step dosing regimen was derived that targeted exposure in infants and children 6 months to 12 years of age to match the penciclovir AUC seen in adults after a 500-mg dose of famciclovir.

Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Antiviral Agents; Body Weight; Capsules; Child; Child, Preschool; Famciclovir; Female; Guanine; Herpes Simplex; Humans; Infant, Newborn; Male; Models, Biological

In a prospective, controlled, and randomized study, we compared the outcome of 101 Bell's palsy patients treated with acyclovir (54 patients) or prednisone (47 patients). The acyclovir dosage was 2400 mg (800 mg three times a day) for 10 days, and prednisone was given as a single daily dose of 1 mg/kg of body weight for 10 days and tapered to 0 over the next 6 days. Minimum follow-up was 3 months in all patients. Patients in the prednisone group had better clinical recovery than those treated with acyclovir. Less degree of neural degeneration was observed in the prednisone group compared with acyclovir patients. The incidence of sequelae was the same in both groups. According to these results, in a 10-day treatment cycle acyclovir given 800 mg three times is not as useful as prednisone given 1 mg/kg of body weight once a day in patients with idiopathic facial nerve paralysis.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anti-Inflammatory Agents; Antiviral Agents; Body Weight; Drug Administration Schedule; Facial Nerve; Facial Paralysis; Female; Follow-Up Studies; Glucocorticoids; Humans; Incidence; Male; Middle Aged; Nerve Degeneration; Prednisone; Prospective Studies; Treatment Outcome

There is limited guidance on the most appropriate dosing strategy for intravenous (IV) acyclovir in obese patients. The manufacturer's labelling suggests using ideal body weight (IBW); however, previous pharmacokinetic studies of obese patients have shown more rapid systemic clearance and lower area under the curve and peak concentrations compared with patients with a body mass index (BMI) < 30 kg/m. This was a retrospective cohort review of adult patients with a BMI ≥ 30 kg/m. In this study, 8.5% of all obese patients receiving acyclovir developed AKI. Further studies are needed to confirm dosing recommendations.

Topics: Acute Kidney Injury; Acyclovir; Adult; Body Weight; Humans; Obesity; Retrospective Studies

Prognosis of herpetic encephalitis remains severe, with a high proportion of deaths and sequelae. Its treatment is based on acyclovir, but the precise and most effective modalities of this treatment are not established. The objective of this study was to determine them.. For this, we carried out a descriptive, retrospective, monocentric study, using the current coding database at Marseille University Hospitals. Cohort was intended to be exhaustive for the disease, from January 2000 to June 2019, including patients hospitalized in intensive care and conventional hospitalization sector. Patients (n = 76) included were at least 16 years of age and had a clinical presentation, cerebral Magnetic Resonance Imaging, and/or electroencephalogram abnormalities consistent with herpetic encephalitis confirmed by a positive HSV-PCR in the CSF. Clinical data and treatment, including the doses actually administered to the patient, were compared according to patient's outcome.. The mortality rate was 12%, whereas 49% had complete recovery and 39% sequelae impeding independence. Poor outcome was statistically associated with persistence of confusion, aphasia, and impaired consciousness lasting more than 5 days, superinfection, status epilepticus, and length of stay in intensive care unit. A statistical decision tree, constructed using the Classification And Regression Tree model, to prioritize treatment management, showed two main factors that influence the outcome: the patient's weight, and the average daily acyclovir dose actually administered.. These results suggest to modify acyclovir management in herpetic encephalitis, for low-weight patients (< 79 kg) with a minimum dosage of 2550 mg/day (850 mg/ 8 h), when possible.

Topics: Acyclovir; Antiviral Agents; Body Weight; Disease Progression; Encephalitis, Herpes Simplex; Humans; Retrospective Studies

Dosing of intravenous acyclovir for herpes encephalitis in obese patients is recommended to be based on ideal body weight. However, limited data support this recommendation, and recent data suggest this may lead to underdosing.. To determine national dosing practices of intravenous acyclovir across a range of patient weights.. A survey was distributed to members of the American College of Clinical Pharmacy Critical Care and Infectious Diseases Practice & Research Networks listservs. Data collected included demographic information and dosing of acyclovir, given consistent patient cases with varying patient weight.. A total of 264 pharmacists participated in the survey, with 240 (90.9%) participants completing the survey. Participants were predominately clinical pharmacists. As patient weight increased, respondents were more apt to dose based on an adjusted body weight, with dosing in the obese and morbidly obese showing a clear lack of consistency.. Intravenous dosing of acyclovir for herpes encephalitis is variable, especially in obese patients, and does not reflect recommendations. Limited data provide conflicting recommendations for dosing in obese patients, and future studies are necessary to optimize patient outcomes and prevent toxicity.

Topics: Acyclovir; Administration, Intravenous; Antiviral Agents; Body Weight; Encephalitis, Herpes Simplex; Female; Humans; Male; Obesity; Pharmacists; Surveys and Questionnaires

Our objective was to study the clinico-pathologic correlations in BK virus nephropathy.. We conducted a retrospective study of all patients with biopsy-proven polyoma (BK) virus infection. We compared their survival and renal outcomes versus BK virus-negative patients with biopsy-proven graft rejection. Histopathologic characterization by a blinded nephropathologist was performed.. BK nephropathy was found in 10 patients biopsied for graft dysfunction. All virus-positive patients received antithymocyte globulin induction therapy compared with only 59.3% of the BK-negative group (P = .06). The percentage of patients in the BK-negative group who received acyclovir was significantly higher than that in the BK-positive group (P = .01). After a mean observation period of 6.8 ± 3.2 years, 70% of the BK group had functioning grafts compared with 68% in the BK-negative group (P = .9) with similar 3-year graft survival in the 2 groups (80% and 90%; P = .8). Within the BK group, graft survival was better in the older group (P = .005) and in those with deceased donor kidney grafts (P = .016). Patients in the BK-negative group were heavier (mean weight of 64.3 ± 12.1 vs 46.7 ± 20.6 kg; P = .003). None of the histopathologic features studied had any effect on renal prognosis.. The risk factors for developing BK nephropathy were use of antithymocyte globulin, lower weight, and not using acyclovir as early prophylaxis. Within the BK nephropathy group, better graft survival was observed in deceased donor kidney recipients and in older patients. The viral load and polyoma virus nephropathy stage did not affect graft survival in this small sample study.

Topics: Acyclovir; Adolescent; Adult; Antilymphocyte Serum; Antiviral Agents; Biopsy; BK Virus; Body Weight; Child; Female; Graft Survival; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Kidney; Kidney Transplantation; Male; Middle Aged; Polyomavirus Infections; Predictive Value of Tests; Retrospective Studies; Risk Factors; Saudi Arabia; Time Factors; Treatment Outcome; Tumor Virus Infections; Young Adult

Simotinib hydrochloride (SIM6802), which is a new epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is often prescribed for cancer patients with comorbidities and has serious adverse effects on gastrointestinal physiology. The drug-drug interactions (DDIs) between simotinib and other drugs in combination and the underlying mechanism of its gastrointestinal toxicity remain unclear. We hypothesized that the DDIs and the gastrointestinal toxicity of simotinib were related to its effects on the permeability of the intestine.. To determine the intestinal absorption capacity, pharmacokinetic studies and an in situ loop assay were used. The intestinal permeability was measured by a Caco-2 Transwell model. Real time PCR and Western blots were applied to detecting the expression changes of cell junction genes.. Our research demonstrated that simotinib upregulated the absorption of cefaclor, valaciclovir and acyclovir. The increase of non-selective absorption was caused by the low expression of cell junction gene afadin-6 and the increase in paracellular permeability in intestinal epithelial cells after simotinib treatment.. These findings revealed that simotinib upregulated intestinal absorption by increasing the paracellular permeability of intestinal epithelial cells. Our research provides theoretical bases for better formulation of EGFR-TKIs to alleviate adverse gastrointestinal effects and also provides guidance for clinical administration of simotinib.

Topics: Acyclovir; Anti-Infective Agents; Body Weight; Caco-2 Cells; Cefaclor; Dose-Response Relationship, Drug; Drug Interactions; Humans; Intestinal Absorption; Intestinal Mucosa; Microfilament Proteins; Permeability; Quinazolines; Spiro Compounds; Up-Regulation; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Body Weight; Drug Therapy, Computer-Assisted; Female; Humans; Infusions, Intravenous; Male; Medical Order Entry Systems; Middle Aged

Epstein-Barr virus (EBV) infection occurring in the postoperative period represents a significant risk for pediatric transplant recipients. It presents in various manners, including a mononucleosis-like syndrome, hepatitis, encephalopathy, or posttransplant lymphoproliferative disease (PTLD). Valacyclovir has in vitro activity against EBV. We sought to review our experience with valacyclovir on peripheral blood EBV viral loads among a group of EBV-infected patients after liver transplantation (OLT).. Twelve children of ages 6-36 months (median, 12 months), underwent OLT. Eight (66%) were EBV immunoglobulin (Ig)G seronegative at the time of the operation. Eight patients developed primary infection and 4 patients developed reactivation of a post primary infection. Valacyclovir was prescribed immediately to 3 patients when we detected an acute-primary EBV infection. Valacyclovir was prescribed for 2 patients who had primary EBV infections followed by PTLD. Three patients who had primary EBV infection were administered valacyclovir after they became chronically EBV PCR positive for more than 1 year. Four out of 12 cases (33%) were EBV seropositive at the time of OLT, and underwent postprimary EBV reactivation displaying chronic EBV carrier state for 8-10 months before valacyclovir treatment. Peripheral blood EBV viral loads were tested every 2 months. The primary outcome was the proportion of subjects with EBV viremia who had a >or=2 log 10 decrease in EBV copies/mL after valacyclovir treatment. The duration of valacyclovir treatment was a median of 10 months (range, 8-11 months). At the beginning of the treatment period the median level of EBV viral load was 1.1 x 10(4) (range, 1 x 10(4) to 1 x 10(7)). EBV virus was cleared in only 1 patient with primary acute EBV infection. EBV viral loads did not change in 7 of 12 patients and decreased only 1 log 10 (n = 2) or 2 log 10 (n = 2).. In this small, non-placebo-controlled study, valacyclovir treatment was not effective to decrease peripheral blood EBV viral loads.

Topics: Acute Disease; Acyclovir; Antiviral Agents; Body Weight; Child, Preschool; Chronic Disease; Epstein-Barr Virus Infections; Humans; Infant; Liver Function Tests; Liver Transplantation; Postoperative Complications; Recurrence; Retrospective Studies; Valacyclovir; Valine; Viral Load; Virus Activation

Herpes simplex virus type 1 (HSV-1) is an important pathogen related to epilepsy. We have shown previously that corneal inoculation of mice with HSV-1 causes acute spontaneous behavioral and electrophysiological seizures and increases hippocampal excitability and kainite-induced seizure susceptibility. In this study, we aimed to determine whether early-life HSV-1 infection in mice might cause short- and long-term enhanced susceptibility to pentylenetetrazol (PTZ)-induced seizures and to evaluate whether early antiviral drug therapy was effectively ameliorating this deficit. Seizure threshold was calculated by the latency of onset of the myoclonic jerk, generalized clonus, and maximal tonic-clonic convulsion. We demonstrate that the localization of viral antigens was predominantly within the bilateral temporal areas (amygdala, piriform, and entorhinal cortex) of HSV-1-infected mice. We also present evidence that mice of all HSV-1-infected groups had a shorter latency and higher severity to PTZ-induced seizures than in age-matched, mock-infected controls. Treatment of HSV-1-infected mice with valacyclovir, a potent inhibitor of HSV-1 replication, produced a dose-dependent decrease in the signs of neurological deficits, pathological damages, and PTZ-induced seizure severity. Our results are consistent with the hypothesis that early-life HSV-1 infection leads to persistent enhancement of neuronal excitability in limbic circuits, which could result in an overall increased propensity to induce seizures later in life. Additionally, prompt optimal antiviral therapy effectively decreases seizure susceptibility in HSV-1-infected mice by limiting the level of viral replication and inflammatory response induced by virus. The present study provides not only experimental evidence, but also a new therapeutic strategy in HSV-1-associated human epilepsy.

Topics: Acyclovir; Animals; Antiviral Agents; Behavior, Animal; Body Weight; Disease Susceptibility; Dose-Response Relationship, Drug; Drug Interactions; Electroencephalography; Electromyography; Herpes Simplex; Herpesvirus 1, Human; Hippocampus; Immunohistochemistry; Infections; Male; Mice; Mice, Inbred BALB C; Pentylenetetrazole; Reaction Time; Seizures; Staining and Labeling; Time Factors; Valacyclovir; Valine; Virus Latency

Mycophenolate mofetil (MMF) is a new immunosuppressive drug used in combination with cyclosporin A (CsA) or tacrolimus and prednisone to prevent rejection of renal allografts in both adult and pediatric recipients. It has been shown in several large studies that MMF significantly decreases the incidence of acute rejection in adults and has acceptable adverse effects. In this retrospective study, we compare the incidence of adverse events between pediatric and adult renal allograft recipients. Twenty-two children and 37 adult renal allograft recipients were included in the study. The initial dose of MMF was 1.5 g b.i.d. for the adult patients and ranged from 15 to 30 mg/kg/d for the pediatric patients. All patients received p.o. acyclovir as prophylaxis for cytomegalovirus (CMV). The two groups were similar regarding gender distribution and graft source. Acute rejections occurred in 10 of the 22 pediatric patients (45%) and in nine of the 37 adults (24%), p = NS. The incidence of infections was similar in both groups except for the occurrence of CMV (n = 5), which was seen only in adults. The incidence of GI symptoms was significantly higher in the pediatric population (54.5% vs. 21.6%; p = 0.02). Significant weight loss was seen more often in the smaller pediatric patients (weight < or = 15 kg) compared to the larger pediatric patients, 60% vs. 11.7%, p = 0.05. Among the patients who had significant GI symptoms 50% of the adults and 75% of the pediatric recipients required either dose reduction or, most commonly, discontinuation of the MMF. The need to discontinue MMF was significantly higher in the pediatric patients, especially in those that weighed less than 15 kg. We suggest the possibility that the optimum dose, dosing interval or preparation of MMF has not yet been established for pediatric patients. One should therefore monitor pediatric patients closely, especially the small ones, to avoid significant nutritional problems and other adverse GI events.

Topics: Acute Disease; Acyclovir; Adolescent; Adult; Age Factors; Antiviral Agents; Body Weight; Child; Child, Preschool; Cytomegalovirus Infections; Data Interpretation, Statistical; Female; Graft Rejection; Humans; Immunosuppressive Agents; Infant; Kidney Transplantation; Male; Mycophenolic Acid

Famciclovir (FCV) and valaciclovir (VACV) have previously been shown to be potent inhibitors of herpes simplex virus type 1 (HSV-1) in a murine cutaneous model. In the present study, mice were inoculated in the skin of the left ear pinna with herpes simplex virus (HSV) type 1. Antiviral therapy was started on different days postinoculation (p.i.), terminating at the end of day 10 p.i. The compounds were administered twice daily by oral gavage at 50 mg/kg of body weight/dose. Mice were sampled on day 5 p.i., during the acute phase of the infection, and the titers of infectious virus in the target tissues (ear, brain stem, and trigeminal ganglia) were determined. At 2 to 3 months p.i., the ipsilateral and contralateral trigeminal and cervical dorsal root ganglia were explanted, and four different methods were used to detect latent HSV. The methods were (i) conventional explant culture for 5 days followed by homogenization, (ii) long-term culture (up to 73 days) of whole ganglia, followed by homogenization, (iii) dissociation by enzymatic disaggregation and an infectious center assay, and (iv) in situ hybridization to detect latency-associated transcripts (LATs). The conventional explant culture method was the least sensitive method, while in situ staining for LAT was the most sensitive, and all mice, including those treated from early times with FCV, were shown to be latently infected. Significantly less latent virus was detected by all four methods, however, in ganglia obtained from mice that had been treated with FCV in comparison with the amount detected in ganglia from mice that had been treated with VACV. However, in no case was latency completely eliminated.

Topics: 2-Aminopurine; Acyclovir; Animals; Antiviral Agents; Body Weight; Brain; Cell Culture Techniques; Dermatitis; Ear; Famciclovir; Female; Herpes Simplex; Herpesvirus 1, Human; In Situ Hybridization; Mice; Mice, Inbred BALB C; Neurons; Trigeminal Ganglion; Valacyclovir; Valine; Virus Latency

The immunosuppressive agent cyclosporin A (CyA) and the antiviral drug acyclovir may cause renal functional impairment. CyA-induced immunosuppression increases the rate of viral infections. Therefore we were interested to determine whether short-term co-administration of CyA and acyclovir involves an increased nephrotoxic risk. Male Wistar rats were treated with CyA (20 mg/kg body wt., s.c., once daily for 8 days), acyclovir (15 mg/kg body wt., s.c., 3-times daily for the last 5 days) or a combination of CyA and acyclovir. Blood levels of CyA were determined after a single dose. Urine was monitored for volume, osmolality, total protein and N-acetyl-beta-D-glucosaminidase (beta-NAG). Concentrations of blood urea nitrogen (BUN) and plasma-creatinine were determined (day 9). Renal cortical slices were monitored for accumulation of weak organic acids (para-aminohippurate, PAH) and bases (tetra-ethylammonium, TEA) and for malondialdehyde (MDA) content. Renal histology was also examined. CyA induced a decrease in body and kidney weight, in urine osmolality and in the excretion of total protein. Plasma-creatinine and BUN as well as MDA content of renal tissues were increased by CyA. Acyclovir alone did not induce significant changes. In comparison to CyA values, urine volume and beta-NAG excretion were enhanced and TEA accumulation depressed by the concomitant administration of CyA and acyclovir. CyA- or acyclovir-treatment alone did not result in significant morphological changes. In the group co-administered CyA/acyclovir, the kidneys showed mild to moderate signs of tubulopathy. Short-term co-administration of CyA and acyclovir was concluded to have possibly increased nephrotoxic potential.

Topics: Acetylglucosaminidase; Acyclovir; Animals; Antiviral Agents; Blood Urea Nitrogen; Body Weight; Creatinine; Cyclosporine; Drug Combinations; Immunosuppressive Agents; Kidney; Kidney Function Tests; Male; Organ Size; p-Aminohippuric Acid; Proteinuria; Rats; Rats, Wistar

1. 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 such an association on rat pregnancy. 2. AZT (60 mg/kg b.w.) and ACV (60 mg/kg b.w.) were given to groups of pregnant rats once a day from the 1st to the 20th day of gestation. 3. Maternal body weight gain was severely affected by ACV; this effect was attenuated in rats treated with AZT+ACV and was virtually absent with AZT alone. 4. The abortive action of ACV was markedly diminished in the group treated with the association AZT+ACV. 5. The deleterious effects of ACV on rat pregnancy are presumably due to its extraplacental actions, and these are, at least in part, counteracted by concomitant treatment with AZT.

Topics: Acyclovir; Animals; Body Weight; Drug Interactions; Embryo Implantation; Female; Fetal Resorption; Fetus; Organ Size; Placenta; Pregnancy; Pregnancy, Animal; Rats; Rats, Wistar; Zidovudine

Five pregnant rats were treated during organogenesis with sc injections of acyclovir (50 mg/kg body weight) on days 9, 10 and 11 of pregnancy. The fetuses (N=62) were evaluated on day 20 of gestation and presented decreased body weight as well as delayed differentiation of fetal rat palate epithelium, with increased nuclear volume, decreased cytoplasmic and cellular volumes, decreased epithelial and keratin thicknesses, and increased cellular numerical density.

Topics: Abnormalities, Drug-Induced; Acyclovir; Animals; Antiviral Agents; Body Weight; Embryonic and Fetal Development; Epithelium; Female; Mouth Mucosa; Palate; Palate, Soft; Pregnancy; Rats; Rats, Wistar; Statistics, Nonparametric; Teratogens

A pilot study was initiated to explore a sequential combination antiretroviral regimen in 21 patients with AIDS or advanced human immunodeficiency virus (HIV) infection, who had received little or no prior anti-HIV therapy. The mean entry CD4 cell count was 184/mm3. Patients received 3-week cycles consisting of zidovudine plus acyclovir, dideoxyinosine, and dideoxycytidine for 1 week each. Overall, the regimen was well tolerated for up to 3 years. The principal toxicities were anemia, nausea, and vomiting; 1 patient developed retinal lesions. The mean CD4 cell count reached a peak of 64 cells/mm3 above baseline at week 8 (P = .005 compared to baseline) and remained above baseline for > 40 weeks. Patients also gained weight and had decreases in serum HIV p24 antigen. Eight patients developed opportunistic infections or tumors. Only 4 patients died during 3 years of follow-up. This regimen appears to be generally tolerable and to have anti-HIV activity. Additional studies will be needed, however, to learn how to best combine the available agents in patients with HIV infection.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Complex; Antigens, CD; Biomarkers; Body Weight; CD4 Antigens; Didanosine; Drug Administration Schedule; Drug Therapy, Combination; HIV Core Protein p24; Humans; Male; Middle Aged; Pilot Projects; T-Lymphocyte Subsets; Time Factors; Zalcitabine; Zidovudine

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

The renal effects of acyclovir (100 mg/kg body weight i.p. for 7 days) were studied in rats. All animals became polyuric and presented an increase in blood urea nitrogen and fractional excretion of sodium and potassium. During hypotonic saline infusion, the acyclovir-treated rats showed higher distal fractional delivery compared to normal rats (27.8 +/- 4.7 vs. 11.3 +/- 0.9%, p less than 0.01) and a lower ratio of free-water clearance to distal sodium delivery (33.5 +/- 7.8 vs. 57.2 +/- 3.9%, p less than 0.02). Following hypertonic saline infusion, the ratio of osmolar to inulin clearance was higher in acyclovir rats (47.8 +/- 7.4%) than in normal rats (27.0 +/- 4.8%), whereas the ratio of free-water reabsorption to osmolar clearance was lower in the acyclovir rats (13.6 +/- 4.6 vs. 38.2 +/- 3.2%, p less than 0.01). These findings suggest an effect of acyclovir on the proximal tubule, thick ascending limb and/or inner medullary collecting duct (IMCD). In vitro measurements of 3H2O permeability of perfused IMCD of normal rats showed that vasopressin (50 microU/ml) added to the bath increased the diffusional water permeability (43.4 +/- 4.8 vs. 105.6 +/- 9.1 x 10(-5) cm/s), while in acyclovir rats, the control value (58.8 +/- 9.1 x 10(-5) cm/s) did not increase significantly in the presence of vasopressin (71.3 +/- 13.6 x 10(-5) cm/s). These results suggest that high doses of acyclovir produce azotemia and an abnormal function of the proximal tubule and thick ascending limb associated with resistance to vasopressin of the IMCD.

Topics: Acyclovir; Animals; Blood Urea Nitrogen; Body Weight; Dose-Response Relationship, Drug; Kidney; Male; Perfusion; Potassium; Rats; Rats, Wistar; Sodium; Vasopressins

Aciclovir (synonym: acyclovir) causes abnormal thymus development in rats. After treatment on day 10 of gestation a weight reduction of the organ is obvious in 21-day-old fetuses which persists postnatally. Adult male rats exposed in utero to one or three injections of 100 mg aciclovir/kg body wt given to the dam on day 10 of pregnancy showed a reduction of the thymus weight to 333 +/- 158 mg and 276 +/- 61 mg (control: 428 +/- 92 mg; n = 10). Corresponding alterations were detectable in female offspring. Liver weight was also decreased and spleen weight (in relation to body wt) was significantly increased in the offspring after the three exposures. In a host resistance model with Trichinella spiralis the function of the immune system of rats prenatally exposed to aciclovir was examined. Six weeks postnatally 10-12 randomly selected male rat offspring of one control and two treatment groups (1 or 3 injections of 100 mg aciclovir/kg body wt on day 10 of gestation) were infected orally with 500 Trichinella spiralis muscle larvae. Before and several times after the infection blood was taken from a tail vein or obtained by decapitation for examination of the antibody titers (IgM, IgG, IgA, IgE) to antigens of T. spiralis. Six weeks after the infection the weight of relevant organs was determined and tongue preparations were used for T. spiralis muscle larvae counting. Aciclovir exposed animals showed a different immune response than control rats. IgM titers in both treatment groups were higher than in controls two weeks after the infection but not different by the end of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acyclovir; Animals; Antibodies, Helminth; Body Weight; Embryonic and Fetal Development; Female; Fetus; Immune System; Injections, Subcutaneous; Male; Mortality; Organ Size; Rats; Rats, Wistar; Thymus Gland; Trichinella spiralis; Trichinellosis

The effect of co-administration of acyclovir and cis-diamminedichloroplatinum(II) (cisplatin) on nephrotoxicity in male Wistar rats was investigated. Animals received acyclovir (15 mg/kg body weight, s.c., three times per day for 5 days) or cisplatin (5 mg/kg body weight, i.p., one single injection) or a combination of both drugs. Acyclovir plasma levels were determined after one single acyclovir s.c. injection. Urines were monitored for volume, pH, osmolality and excretion of N-acetyl-beta-D-glucosaminidase (NAG), lysozyme and total protein. Concentrations of blood urea nitrogen and plasma creatinine were determined on day 6. Renal cortical slices were monitored to assess the accumulation of weak organic bases (tetraethylammonium) and acids (p-aminohippurate). Cisplatin induced a marked increase in the excretion of NAG, lysozyme and total protein and an increase in urine volume, plasma creatinine and blood urea nitrogen. Urine osmolality and accumulation of p-aminohippurate were depressed by cisplatin. Acyclovir treatment alone caused no significant symptoms of nephrotoxicity. Co-administration did not impair renal function more than cisplatin treatment alone, excepting a slight rise in lysozyme excretion on day 6. Short-term antiviral therapy with acyclovir, concomitant to cisplatin treatment, may bring, if at all, a slightly increased nephrotoxic risk.

Topics: Acyclovir; Animals; Body Weight; Cisplatin; Creatinine; Drug Synergism; Kidney; Male; Muramidase; Organ Size; Rats; Rats, Inbred Strains

Disseminated cytomegalovirus (CMV) infection is a common complication of acquired immunodeficiency syndrome and contributes significantly to its morbidity and mortality. Ganciclovir, a guanosine analogue, inhibits CMV replication in vitro and in vivo, and its use can stabilize the clinical course of an affected patient. We examined the changes in body composition that occurred in four untreated patients and in eight patients who were treated with ganciclovir for serious CMV infections. Untreated patients lost weight, depleted body cell mass, as determined from total-body potassium measurements in a whole-body counter, lost body fat, as estimated from anthropometric measurements, and had a progressive fall in serum albumin concentration. In contrast, treated patients gained weight, repleted body cell mass and body fat, and increased serum albumin concentration during a three-month follow-up. In this study, it was estimated that ganciclovir therapy resulted in a net energy conservation of 2629 kJ/d. The ability to promote body cell mass repletion may be considered a demonstration of the efficacy of ganciclovir in the treatment of serious CMV infections in patients with acquired immunodeficiency syndrome.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Body Constitution; Body Weight; Cytomegalovirus Infections; Ganciclovir; Humans; Middle Aged; Nutrition Disorders; Prospective Studies; Retrospective Studies; Serum Albumin

Following three s.c. injections of acyclovir (100 mg acyclovir/kg) into rats on day 10 of pregnancy 19 litters were evaluated on day 21 of gestation and the effects were compared to the results obtained from controls (nine litters) which received the vehicle (0.1 N NaOH) only. The following results were obtained (treated group versus control group): 1) Implantations/litter: 11.2 +/- 1.3 versus 10.2 +/- 1.1; 2) resorptions/implantations: 27.7% versus 2.2%; 3) number of viable fetuses evaluated: 154 versus 90; 4) fetuses with anomalies of the skull: 78% versus 12%; 5) fetuses with anomalies of the vertebral column: 38% versus 13%; 6) gross-structural anomalies predominantly affected the skull and tail. The most frequently registered defects were: os tympanicum (smaller): 23%, os tympanicum (missing): 23%; missing tail: 7%; protruding tongue (15%); none of these defects were seen in the control fetuses. Postnatally we observed a high mortality rate among the offspring. From a total of 85 newborn (nine litters) we obtained 73 viable offspring (9.1 +/- 3.4); 81% of them had tail alterations. In the control group of eight litters (9.4 +/- 2.3) no tail alterations occurred. On day 21 postnatally 40 viable offspring were alive (mortality rate: 38.8%). Nearly all of these animals had visible alterations at multiple sites of their bodies; most frequently observed were: tail impairment, closed eyes, dragging hind-limbs, and urogenital alterations (e.g. testicular atrophy). These studies how for the first time that prenatal treatment with acyclovir induces gross-structural defects which persist postnatally.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abnormalities, Drug-Induced; Acyclovir; Animals; Body Weight; Female; Litter Size; Maternal-Fetal Exchange; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred Strains; Teratogens

The antiviral activity of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) against guinea pig cytomegalovirus (GPCMV) was evaluated in guinea pig cell cultures and in Hartley guinea pigs. The 50% effective dose of DHPG against GPCMV replication in cell cultures was 71 microM. Ultrastructural studies revealed that DHPG inhibited the formation of viral cores and the production of nucleocapsids, enveloped virions and dense bodies, but the drug did not prevent the formation of virus induced intranuclear tubular structures. In vivo, guinea pigs inoculated intraperitoneally with GPCMV were treated with DHPG, 25 mg/kg subcutaneously, twice daily. Treatment was initiated 24 h after infection and continued for 7 days. During the acute infection, the average body weights of DHPG-treated, virus infected guinea pigs were approximately 14% lower than the sham-treated counterparts on day 10, 11 and 13 post-virus inoculation. Virus infectivity titers were higher in the lungs of DHPG-treated guinea pigs on day 10 than the sham-treated ones. Although there was no significant difference on histopathologic lesions in the spleen, liver and lungs of the drug-treated and the sham-treated guinea pigs, DHPG treated animals appeared to have fewer virus-induced lesions or inclusions in the kidneys and salivary glands than the sham-treated ones. In addition, virus infectivity titers in the salivary gland of DHPG treated guinea pigs were consistently lower than the sham-treated animals.

Topics: Acyclovir; Animals; Antiviral Agents; Body Weight; Cells, Cultured; Cytomegalovirus; Cytomegalovirus Infections; Cytopathogenic Effect, Viral; Ganciclovir; Guinea Pigs; Microscopy, Electron; Morphogenesis; Virus Replication

Topics: Acyclovir; Administration, Oral; Administration, Topical; Body Weight; Drug Resistance, Microbial; Half-Life; Herpesviridae; Humans; Kinetics

Compound BW759 (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine) was shown to be about 230 times more active than acyclovir (9-[2-hydroxyethoxymethyl]guanine) (ACV) against Equid herpesvirus type 1 infection in Syrian hamsters and was more effective against Aujeszky's disease in mice. The therapeutic superiority of BW759 over ACV was greater than expected from quantitative inhibitory results in tissue culture with these viruses. When administered to hamsters at dose rates sufficient to prevent any Equid herpesvirus type 1-induced mortality (100 mg of ACV per kg per day; 3 mg of BW759 per kg per day), BW759 inhibited viral multiplication, as judged by histopathological observations, clinical chemistry, and liver virus concentrations, to a greater extent than ACV. Compound BW759 was particularly effective when administered via the oral route. The reasons for the superiority of BW759 over ACV remain to be elucidated.

Topics: Acyclovir; Alkaline Phosphatase; Animals; Antiviral Agents; Body Weight; Cricetinae; Ganciclovir; Herpesviridae Infections; Herpesvirus 1, Equid; Liver; Male; Mesocricetus; Mice; Mice, Inbred Strains; Pseudorabies