Oral, subcutaneous, and intramuscular bioavailabilities of the antiviral nucleotide analog 9-(2-phosphonylmethoxyethyl) adenine in cynomolgus monkeys.
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.
Cundy
K C
KC
Gilead Sciences, Inc., Foster City, California 94404.
Shaw
J P
JP
Lee
W A
WA
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D001825:Body Fluid Compartments; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D005260:Female; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008252:Macaca fascicularis; D008297:Male; D063065:Organophosphonates
D000998:Antiviral Agents; D002250:Carbon Radioisotopes; D063065:Organophosphonates; C053001:adefovir; D000225:Adenine