Acyclovir concentrations and tolerance during repetitive administration for 18 days.
Acyclovir, a new antiherpetic agent, was administered for 18 days to 10 recipients of bone marrow transplants as a part of a double-blind, randomized, placebo-controlled trial assessing its prophylactic efficacy and safety. Renal glomerular function diminished over the time of the study in the 10 acyclovir-treated and 10 placebo-treated patients. The decline in glomerular filtration rate (GFR) did not differ significantly between the two groups and is unlikely to be associated with acyclovir. The pharmacokinetics of acyclovir is expected to be altered by a change in GFR since glomerular filtration is probably the major process involved with the excretion of acyclovir. Such an alteration was seen as an increase over time of both peak (one hour after the end of an infusion) and trough (immediately before a dose) plasma acyclovir concentrations. Although peak and trough acyclovir concentrations rose from 8.5 to 15.8 microM and from 1.7 to 4.1 microM, respectively, these rises are fully attributable to the decreases in GFR seen in both drug- and placebo-treated groups. The placebo-controlled and blinded nature of this trial allows an assessment of the effects of acyclovir on a battery of hematologic, renal, and hepatic tests. The only adverse effects observed that statistically differed in the acyclovir-treated group compared with controls were the rises in SGOT (53.2 +/- (SEM) 19.9 versus 3.1 +/- 12.2) and SGPT (59.7 +/- 15.3 versus 12.3 +/- 13.8).
D000212:Acyclovir; D000998:Antiviral Agents / Q000009:adverse effects / Q000097:blood*; D001772:Blood Cell Count; D016026:Bone Marrow Transplantation; D004341:Drug Evaluation; D005919:Glomerular Filtration Rate; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D006561:Herpes Simplex / Q000517:prevention & control*; D006801:Humans; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology
D000998:Antiviral Agents; D006147:Guanine; D000212:Acyclovir