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 mumol/L, respectively. The pharmacokinetic model predicted acyclovir concentrations with a precision of 4.1 mumol/L and bias of -1.19 mumol/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.
Fletcher
C V
CV
Department of Pharmaceutical Services, University of Minnesota, Health Sciences Center, Minneapolis.
Chinnock
B J
BJ
Chace
B
B
Balfour
H H
HH
D000212:Acyclovir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012449:Safety; D013997:Time Factors
D000212:Acyclovir