Reproductive toxicology profile of emtricitabine in mice and rabbits.

Reproductive and developmental toxicology studies were conducted with emtricitabine, a nucleoside analog in development for treatment of human immunodeficiency virus (HIV) (Phase III) and hepatitis B (HBV) (Phase III) infections. Oral doses up to 1000 mg/kg/day provided daily area under the curve (AUC(0-->24)) exposure to pregnant animals approximately 60- (mice) to 120-fold (rabbits) higher than that in humans at the recommended dose of 200 mg given once per day. In a mouse fertility study, emtricitabine had no effect on fertility, sperm count, or early embryonic development.

Efficacy of topical acyclovir monophosphate, acyclovir, or penciclovir in orofacial HSV-1 infections of mice and genital HSV-2 infections of guinea pigs.

The purpose of these studies was to compare the efficacy of acyclovir monophosphate (ACVMP), acyclovir (ACV), or penciclovir (PCV) against HSV-1 in an orofacial infection of mice and against ACV sensitive and resistant genital HSV-2 infections of guinea pigs. Treatment was initiated 24, 48, or 72 hours post inoculation with 5% ACVMP, 5% ACV (Zovirax) or 1% PCV (Denavir). In all experiments, similar efficacy was obtained for ACVMP and ACV, whereas PCV was considerably less effective.

Screening for potential toxicity of antiviral therapies.

Preclinical screening for the toxicity of antiviral drugs has thus far proven quite successful. Twenty-three antivirals spanning a variety of chemical classes and including a combination product, have been safely developed and are listed in the 1999 Physician's Desk Reference. Several of these antivirals have been administered for many years and in various combinations and we are currently unaware of any being withdrawn for safety-related reasons.

Safety assessment, in vitro and in vivo, and pharmacokinetics of emivirine, a potent and selective nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1.

Emivirine (EMV), formerly known as MKC-442, is 6-benzyl-1-(ethoxymethyl)-5-isopropyl-uracil, a novel nonnucleoside reverse transcriptase inhibitor that displays potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity in vivo. EMV showed little or no toxicity towards human mitochondria or human bone marrow progenitor cells. Pharmacokinetics were linear for both rats and monkeys, and oral absorption was 68% in rats.