Maxim Livingston
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Similar to Acyclovir / Aciclovir, antibiotics both 8-hydroxyAcyclovir / Aciclovir and CMMG historical dose-independent kinetics with apparent elimination half-lives of 1-1.6 hr. The elimination of Acyclovir / Aciclovir after antibiotics oral administration was monophasic, with an apparent half-life of 1.3-1.5 hr. Metabolic fate and pharmacokinetics of the Acyclovir / Aciclovir prodrug valAcyclovir acyclovir contraceptive pills / Aciclovir in cynomolgus monkeys.ValAcyclovir / Aciclovir, the L-valyl janessa of Acyclovir / Aciclovir (ZOVIRAX), demonstrated good oral absorption and nearly complete conversion to Acyclovir / Aciclovir in cynomolgus monkeys, indicating its suitability as an orally administered genital herpes prodrug. Intravenously administered [8-14C]valAcyclovir / Aciclovir (10 mg/kg) was rapidly converted to Acyclovir / Aciclovir, with the elimination half-life of Acyclovir / Aciclovir (0.9 hr) being 1.5-fold that of the prodrug (0.6 hr). The oral bioavailability of Acyclovir / Aciclovir derived from valAcyclovir aldara / Aciclovir in cynomolgus monkey was 67 /- 13%, representing a significant improvement over the limited bioavailability after Acyclovir / Aciclovir administration to primates.. Dose-independent kinetics were observed for Acyclovir / Aciclovir derived from orally administered [8-14C]valAcyclovir / Aciclovir at the 10 and 25 mg/kg dose levels, with both AUC (24 and 60 microM.hr, respectively) and Cmax (8 and 23 microM, respectively) increasing nearly in proportion to the dose. Following oral and intravenous dosing, intact prodrug accounted for only 0.5% and 6% of urinary radioactivity, respectively. Acyclovir / Aciclovir was present in plasma at all sampling times (5 min to 7 hr postdose) after both oral doses, whereas the prodrug was not detected following either oral dose. The major urinary metabolites of [8-14C]valAcyclovir / Aciclovir, administered orally (10 and 25 mg/kg) or intravenously (10 mg/kg) to male monkeys, were Acyclovir / Aciclovir (46%-59% of urinary radioactivity), 8-hydroxyAcyclovir / Aciclovir (25%-30%), and 9-(carboxymethoxymethyl)guanine (CMMG) (11%-12%).
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