Metabolic disposition of acyclovir in the guinea pig, rabbit, and monkey

Two guinea pigs and two rabbits were each inoculated subcutaneously with 14C-labeled acyclovir (25 mg/kg). Both species excreted the entire amount within 72 hours. The rabbits excreted all of the radioactivity in the urine while the guinea pigs excreted an average of 14.2 percent in the feces. The rabbits excreted an average of 71.0 percent of the dose as unchanged drug; 25.1 percent was excreted as 9-carboxymethoxymethylguanine (CMMG) and 3.5 percent as 8-hydroxy-9-(2-hydroxyethoxymethyl)guanine (8-hydroxyacyclovir). An average of 60.7 percent of the dose was recovered from the guinea pigs as acyclovir; 32.3 percent was excreted as CMMG and 3.1 percent as 8-hydroxyacyclovir. The two rabbits showed elimination-phase half-lives (t 1/2 beta) for plasma acyclovir of 0.8 and 2.2 hours. Mean t 1/2 beta for acyclovir in two rhesus, four patas, and four african green monkeys, each receiving acyclovir (10 mg/kg) as a bolus intravenous injection, were 1.2, 1.7, and 1.8 hours respectively. The average 48 hour urinary excretion of acyclovir, 8-hydroxyacyclovir, and CMMG in the rhesus monkey was estimated to be 21.3 percent, 15.3 percent, and 7.1 percent, respectively, of the total administered amount. The patas and african green species excreted the dose mostly as acyclovir and CMMG.