title: Evaluation of valaciclovir dosage reduction in continuous ambulatory peritoneal dialysis patients.
abstract: In continuous ambulatory peritoneal dialysis (CAPD) patients, acyclovir-induced neurotoxicity is reported to be associated with high serum drug levels even when following the recommended reduced doses for this renal failure population. In view of the high oral bioavailability of valaciclovir (the L-valyl ester of acyclovir) the risk of neurotoxicity becomes more prominent. The present study was conducted in 12 CAPD patients who were administered a single oral dose of 500 mg valaciclovir. Acyclovir was analyzed by high-performance liquid chromatography. Relative pharmacokinetic parameters were estimated based on acyclovir concentrations at 8, 12 and 24 h post-dose. High inter-patient variations were observed with acyclovir apparent total clearance 7.238 +/- 4 l/h and half-life (T1/2) 22.27 +/- 16.82 h. However, dosage simulations confirmed supratherapeutic acyclovir concentrations for all participants when following the recommended dose of 1,000 mg valaciclovir/24 h for varicella zoster infections.
authors.affiliation: School of Pharmacy, University of London, UK. fsc@otenet.gr
authors.forename: F
authors.initials: F
authors.lastname: Stathoulopoulou
authors.forename: S
authors.initials: S
authors.lastname: Dhillon
authors.forename: H
authors.initials: H
authors.lastname: Thodis
authors.forename: C
authors.initials: C
authors.lastname: Stathakis
authors.forename: V
authors.initials: V
authors.lastname: Vargemezis
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D005260:Female; D006562:Herpes Zoster / Q000188:drug therapy*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir