Pharmacokinetics in mice of the anti-retrovirus agent 9-(2-phosphonylmethoxyethyl)adenine.
The pharmacokinetics of 9-(2-phosphonylmethoxyethyl)adenine (PMEA), a potent inhibitor of retrovirus (i.e. human immunodeficiency virus) replication was determined in mice. Upon iv bolus administration of PMEA at 25, 100, or 500 mg/kg, PMEA was rapidly cleared from the plasma in a monoexponential and dose-independent manner (half-life, 7-12.5 min; distribution volume, 0.30-0.36 liter/kg; total body clearance, 1.21-2.41 liters/hr/kg). Irrespective of the initial PMEA dose, 67% of unchanged PMEA was recovered from the urine of mice within 24 hr after administration of PMEA. [3H]PMEA, administered as an iv bolus injection, mainly accumulated in the kidney, liver, and lungs. Significant amounts of monophosphorylated PMEA were detected in kidney and liver, but not other tissues, at 10, 30, and 60 min after iv administration of PMEA. Low but significant levels of PMEA were attained in the brain.
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
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L
Naesens
J
J
Balzarini
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E
De Clercq
D000225:Adenine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D063065:Organophosphonates; D012190:Retroviridae / Q000187:drug effects*; D014018:Tissue Distribution
D000998:Antiviral Agents; D063065:Organophosphonates; C053001:adefovir; D000225:Adenine