In vivo disposition of prostaglandin E1 via pharmacokinetic characterization of its pulmonary metabolite.
Prostaglandin E1 (PGE1) was administered intravenously to conscious beagles and the plasma concentrations of its pulmonary metabolite 13,14-dihydro-15-keto-PGE1 were quantitated at various times after dosing. Pharmacokinetic parameters were calculated for four experimental designs including single-dose bolus injections (30, 10, and 3 micrograms PGE1/kg): single-dose, 4-h continuous infusions (20 and 320 ng/kg/min): multiple-dose continuous infusions (5, 20, 80, and 320 ng/kg/min); and single-dose, 30-day chronic infusions (100 ng/kg/min). 13,14-Dihydro-15-keto-PGE1 plasma concentrations were proportional to the dose in all experiments and they declined biexponentially with a terminal half-life ranging from 25 to 34 min. Typical clearance values were 10-14 ml/kg/min. Pharmacokinetic characterization of 13,14-dihydro-15-keto-PGE1 provides a useful index to monitor, indirectly, the in vivo disposition of PGE1 under clinically and toxicologically relevant circumstances. The factors that prevent accurate or meaningful measurement of intact drug, namely instantaneous and comprehensive pulmonary metabolism, contribute to and simplify the measurement and pharmacokinetic characterization of 13,14-dihydro-15-keto-PGE1.
D000527:Alprostadil / Q000031:analogs & derivatives; D000818:Animals; D001711:Biotransformation; D004285:Dogs; D006207:Half-Life; D007263:Infusions, Parenteral; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D011458:Prostaglandins E / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism*
D011458:Prostaglandins E; C036808:13,14-dihydro-15-ketoprostaglandin E1; D000527:Alprostadil