Pharmacokinetics and tolerance of acyclovir, a new anti-herpesvirus agent, in humans

The pharmacokinetics and tolerance of acyclovir administered intravenously in single doses of 2.5, 5.0, 10.0, and 15.0 mg/kg were studied in 13 volunteers. The mean concentrations (± standard deviations) at the end of infusion as measured by radioimmunoassay were 4.52 ± 0.31, 8.28 ± 2.61, 14.6 ± 2.30, and 22.7 ± 10.4 μg/ml, respectively. Drug elimination during and after the infusion of acyclovir was well described by a two-compartment open model. The mean terminal plasma half-life for each of the groups was 2.85, 2.80, 3.30, and 2.38 h, respectively. Within 72 h after the start of the infusion, 70% of the administered drug was recovered in the urine as unchanged acyclovir. The renal clearance of acyclovir accounted for about 77% of the total clearance and was about threefold greater than the creatinine clearance. This confirms that acyclovir is eliminated predominantly by the kidneys in patients with normal renal function and suggests that renal secretion and glomerular filtration may both be involved. The only adverse effect found by clinical and laboratory monitoring was irritation at the intravenous site after extravasation (in two cases), which resolved without significant sequelae.