Pharmacokinetics of single and multiple doses of oral aciclovir, an antiviral drug.

The singie and multiple dose pharmacokinetics of orally administered aciclovir (ACV) were studied in 19 healthy Japanese male volunteers, Eight men were each . given either a single tablet, of 200 mg (group 1) or 400 mg (group 2).Additionally, 8men, including 5 in group 2, were given a 200-mg tablet every 4 hr 5 times daily and 8hr after the finai administration for a total of 15 doses (3days).In the single-dose study, the plasma ACV concentration increased dose-dependently, and Cmax was 2.80 ±0.30and3.76±0.75μMatTmax of 1.31±0.46and1.50±0.38 hr in groups 1 and 2, respectively. Thereafter, the ACV level monoexponentially decreased with a T1/2 of 2. 51±0. 30 and 2. 56±0. 28 hr in groups 1 and 2, respectively. This process fitted the one-compartment model. The AUC was significantly greater in group 2 (17.62 μmol·hr/l) than that in group 1 (11.72, μmol·hr/l).Renal clearance was similar in both groups (301±23 and 297±42ml/min in groups 1 and 2, respectively). These clearances exceeded the normal glomerular filtration rate, indicating tubular secretion of ACV in addition to glomerular filtration. The mean urinary elimination of unchanged ACV in the two groups was 25.0% and 18.6% of the administered dose within 48 hr, respectively. The total urinary elimination of metabolite (9-carboxy methoxymethylguanine, CMMG) in group 2 was less than 1.4% of the administered dose within 48 hr. In the multiple-dose study, the plasma ACV concentration almost reached a steady state after the fifth administration, and the mean maximum and mini - mum plasma ACV concentrations were in the range of 3.41-3.76μM and 1.08-1.17μM, respectively. The simulation using the parameters obtained from group 1 was applied to the multiple-dose study and showed a good fit with the results obtained. All results seen in 8 subjects were within the 95 % confidence level. The mean urinary elim ination of unchanged ACV was 23.5% of the administered dose within 96 hr. No signi - ficant clinical or laboratory evidence of dose-related toxicity was noted in the 19 sub jects examined.