Acute neurotoxicity following the administration of the recommended or
al dose of acyclovir (800 mg twice daily) to dialysis-dependent patien
ts is increasingly recognised. This suggests that the recommended dose
is too high. Little is known of the pharmacokinetics of oral acyclovi
r in dialysis patients, We studied 7 patients with oliguric end stage
renal failure receiving haemodialysis. Following haemodialysis, each p
atient received a single 800-mg tablet of acyclovir. Plasma acyclovir
levels were monitored over the next 48 h as well as before and after t
he next routine dialysis. Peak plasma levels were achieved at 3 h (12.
54 +/- 1.76 mu M, range 8.5-17.5 mu M) with the half-life calculated t
o be 20.2 +/- 4.6 h. Mean plasma levels of 6.29 +/- 0.94 mu M were wit
hin the quoted range to inhibit herpes tester virus (4-8 mu M) 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 su
ggests that a loading dose of 400 mg acid a maintenance dose of 200 mg
twice daily is sufficient to maintain a mean plasma acyclovir level o
f 6.4 +/- 0.8 mu M A further loading dose (400 mg) after dialysis woul
d raise the residual acyclovir concentration by 6.1 +/- 1.0 mu M. Such
a dose modification should prevent neurotoxicity, whilst the rapid el
imination of acyclovir by a single haemodialysis treatment provides bo
th a diagnostic and therapeutic tool when toxicity is suspected.