Pharmacokinetics and safety of high‐dose oral acyclovir for suppression of cytomegalovirus disease after renal transplantation

The pharmacokinetics and safety of high‐dose oral acyclovir for suppression of cytomegalovirus disease were evaluated in 12 patients undergoing renal transplantation. A 12‐week course beginning 24 hours before transplantation was administered in doses of 800 to 3200 mg/day based on renal function. Acyclovir plasma concentrations were measured by RIA on posttransplant days 1 or 2 and 5, 6, or 7. Mean peak and trough concentrations on days 5, 6, or 7 were 25 and 18 μmol/L, respectively. The pharmacokinetic model predicted acyclovir concentrations with a precision of 4.1 μmol/L and bias of —1.19 μmol/L. Estimates of individual pharmacokinetic parameters were consistent with literature and a priori values. Two of six adverse events were attributable to acyclovir; both resolved with dose modification. The dosage adjustment scheme and pharmacokinetic model performed well, allowing us to safely administer high‐dose oral acyclovir immediately after renal transplantation. We are proceeding with a placebo‐controlled study to assess efficacy for suppression of posttransplant cytomegalovirus disease. Clinical Pharmacology and Therapeutics (1988) 44 , 158–163; doi: 10.1038/clpt.1988.131