title: Avoiding acyclovir neurotoxicity in patients with chronic renal failure undergoing haemodialysis.
abstract: Acute neurotoxicity following the administration of the recommended oral dose of acyclovir (800 mg twice daily) to dialysis-dependent patients is increasingly recognised. This suggests that the recommended dose is too high. Little is known of the pharmacokinetics of oral acyclovir in dialysis patients. We studied 7 patients with oliguric end stage renal failure receiving haemodialysis. Following haemodialysis, each patient received a single 800-mg tablet of acyclovir. Plasma acyclovir levels were monitored over the next 48 h as well as before and after the next routine dialysis. Peak plasma levels were achieved at 3 h (12.54 +/- 1.76 microM, range 8.5-17.5 microM) with the half-life calculated to be 20.2 +/- 4.6 h. Mean plasma level of 6.29 +/- 0.94 microM were within the quoted range to inhibit herpes zoster virus (4-8 microM) at 18 h. Haemodialysis (4-5 h) eliminated 51 +/- 11.5% of the acyclovir which remained at 48 h. Computer modelling of various dose modifications suggests that a loading dose of 400 mg and a maintenance dose of 200 mg twice daily is sufficient to maintain a mean plasma acyclovir level of 6.4 +/- 0.8 microM. A further loading dose (400 mg) after dialysis would raise the residual acyclovir concentration by 6.1 +/- 1.0 microM. Such a dose modification should prevent neurotoxicity, whilst the rapid elimination of acyclovir by a single haemodialysis treatment provides both a diagnostic and therapeutic tool when toxicity is suspected.
authors.affiliation: Department of Nephrology, Royal London Hospital, London, UK.
authors.forename: M K
authors.initials: MK
authors.lastname: Almond
authors.forename: S
authors.initials: S
authors.lastname: Fan
authors.forename: S
authors.initials: S
authors.lastname: Dhillon
authors.forename: A M
authors.initials: AM
authors.lastname: Pollock
authors.forename: M J
authors.initials: MJ
authors.lastname: Raftery
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D003198:Computer Simulation; D005260:Female; D006207:Half-Life; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009420:Nervous System / Q000187:drug effects*; D006435:Renal Dialysis; D014777:Virus Diseases / Q000150:complications / Q000188:drug therapy
chemical_list: D000212:Acyclovir