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Intravenous, subcutaneous, intramuscular, and oral pharmacokinetics of the antiretroviral nucleotide analog [9-(2-phosphonylmethoxyethyl)adenine] (PMEA) were examined in a crossover study with four cynomolgus monkeys using 14C-labelled drug at 10 mg/kg of body weight (20 microCi/kg). Plasma radioactivity declined biexponentially following intravenous administration. Radiochromatography of plasma revealed an absence of PMEA metabolites. Intramuscular and subcutaneous bioavailabilities of PMEA were (means +/- standard deviation) 126% +/- 30% and 101% +/- 25%, respectively, supporting the clinical utility of these routes. The oral bioavailability of PMEA in this species (4.0% +/- 1.0%) appeared to be limited by intestinal permeability and is likely to be equally low in humans.

Oral, subcutaneous, and intramuscular bioavailabilities of the antiviral nucleotide analog 9-(2-phosphonylmethoxyethyl) adenine in cynomolgus monkeys