acyclovir and Anuria

The metabolic disposition and pharmacokinetics of acyclovir have been studied as part of the clinical evaluation of the drug in humans. Data from 10 studies have been summarized and, when appropriate, pooled across studies for further analysis. The principal findings are as follows: Renal excretion is the major route of elimination of acyclovir and is dependent, in part, on active tubular secretion. Total body clearance (Cltot) and half-life are dependent on renal function as evaluated by estimated creatinine clearance (Clcr). Cltot is markedly reduced in the anuric patient. Plasma protein binding is low and drug interactions involving binding displacement are not anticipated. Acyclovir levels in cerebrospinal fluid are approximately 50 percent of corresponding plasma levels. Dose-independent pharmacokinetics is observed in the range of 0.5 to 15 mg/kg. Proportionality between dose and plasma levels is seen after single doses or at steady state after multiple dosing. Similar plasma levels are achieved in adults and pediatric patients (greater than 1 year) when equivalent doses are given based on body surface area. Intrasubject variability of acyclovir disposition is low. Much but not all intersubject variability in Cltot can be explained by differences in renal function. Dosage adjustment for various stages of renal impairment are proposed based on the observed relationship between Cltot and Clcr.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Anuria; Blood Proteins; Child; Child, Preschool; Creatinine; Drug Interactions; Female; Guanine; Humans; Infant; Infant, Newborn; Kidney Tubules; Kinetics; Male; Middle Aged; Models, Biological; Probenecid

We present a critically ill patient with severe renal failure and anuria who underwent hemodialysis (HD), continuous veno-venous hemodialysis (CVVHD) and continuous veno-venous hemodiafiltration (CVVHDF) at different occasions, with 2 commonly used high-efficiency dialyzers (F-8 and CA-210), while receiving i.v. acyclovir. We estimate that during 24 hours of CVVHD with F-8 dialyzer approximately 18% and during 24 hours of CVVHDF with CA-210 dialyzer approximately 65% of the daily administered acyclovir is removed. This is comparable to the amount removed during 4 6 hours of HD, as reported previously. The percentage acyclovir extraction was 84% and 60% during CVVHD and CVVHDF with F-8 and CA-210 dialyzers, respectively. Acyclovir clearance during CVVHD was 14 ml/min and during CVVHDF was 17 ml/min, with F-8 and CA-210 dialyzers, respectively. Acyclovir half-life was 22.5 and 25.5 hours in 2 occasions off any type of renal replacement therapy, and it was 19.5 hours during CVVHDF with CA-210 dialyzer.

Topics: Acute Kidney Injury; Acyclovir; Anuria; Female; Hemofiltration; Humans; Kidney Transplantation; Middle Aged; Renal Dialysis; Transplantation, Homologous

The history of a young female patient is presented. She developed urine retention of sudden onset as a complication of herpes zoster infection manifested in the sacral dermatomes. Symptomatic and antiviral treatments were introduced with full recovery of bladder function. The correct diagnosis of this rare and benign complication of herpes zoster infection can help to avoid unnecessary and invasive examinations.

Topics: Acyclovir; Adolescent; Anuria; Female; Herpes Zoster; Humans; Inosine Pranobex

The pharmacokinetic disposition of acyclovir was studied in six patients with chronic renal failure (CRF) and anuria. At the end of a one-hour intravenous infusion (2.5 mg/kg), the mean peak acyclovir plasma level (+/- SD), determined by radioimmunoassay, was 37.5 +/- 24.2 microM (8.4 +/- 5.4 microgram/ml), twice the level found at this dose in patients with normal renal function (NRF). In the CRF volunteers, significant plasma levels (3.0 +/- 1.4 microM) persisted at 47 hours after drug administration (before hemodialysis) whereas in the NRF patients levels dropped to less than 1 microM by 11 hours. Hemodialysis was started 47 hours after infusion and was continued for six hours. The pre-dialysis plasma drug level was reduced by 61.5 percent at 0.25 to 1.5 hours after the end of dialysis. The mean plasma t 1/2 during dialysis of 5.4 hours, the extraction ratio of 0.44, and the dialysis clearance for plasma of 113 ml/min indicate that acyclovir is efficiently removed by hemodialysis. One-half the suggested intravenous dose for a particular indication can be given every 24 hours and a similar replacement dose should be given after each dialysis.

Topics: Acyclovir; Antiviral Agents; Anuria; Guanine; Humans; Kidney Failure, Chronic; Kinetics; Renal Dialysis