CLINICAL PHARMACOKINETICS OF ORAL ACYCLOVIR IN PATIENTS ON CONTINUOUSAMBULATORY PERITONEAL-DIALYSIS

It is increasingly recognised that dose adjustment of oral acyclovir i n continuous ambulatory peritoneal dialysis (CAPD) patients is necessa ry to avoid neurotoxicity. A single 800-mg oral dose of acyclovir was administered to 10 uninfected anuric patients who were treated by CAPD . Serial blood and CAPD bag samples were analysed for acyclovir during the 31 h after dosing. Serum acyclovir levels were measured using rad ioimmunoassay and the pharmacokinetic parameters were estimated by lin ear regression using the STRIPE computer programme. Peak plasma levels of 8.95 +/- 3.95 mu M were achived at 4.1 +/- 1.85 h with the T1/2 ca lculated to be 14.52 +/- 3 h. The mean predicted serum acyclovir level s at steady state after 1,600-, 800- and 600-mg daily doses were 13.76 , 6.88 and 5.16 mu M, respectively. The present recommended daily dose s of acyclovir (1,600 mg) for end-stage renal disease patients leads t o supratherapeutic levels therefore increasing the risk and incidence of neurotoxicity. Computer modelling of various dosage simulations sug gests that dally doses of 800 and 600 mg will achieve therapeutic leve ls (4-8 mu M).