Pharmacokinetics and pharmacodynamics of radio-labeled iloprost in elderly volunteers.
The plasma levels and excretion of tritium-labeled iloprost in healthy elderly male and female volunteers have been measured after i.v. infusion of 2 ng X kg-1 X min-1 for 4 h and oral administration of 0.1 and 0.48 microgram/kg. During infusion, a steady-state of labeled compounds in the plasma was not achieved. Total radioactivity declined from a mean of 408 pg equiv/ml in three phases, with half-lives of 24 min, 1.7 h and 5.0 h, respectively. A steady-state of unchanged iloprost was reached rapidly with a peak of 81 pg/ml. Plasma levels declined biphasically with half-lives of 6 min and 31 min. Total clearance was 24 ml X min-1 X kg-1. Maximum concentrations of labeled substances after oral administration were 307 and 1,051 pg equiv/ml after 29 and 39 min, respectively. The peak of unchanged iloprost (116 pg/ml) was observed 7.5 min after an oral dose of 0.48 microgram/kg. Bioavailability was 16%. Iloprost was totally metabolized and the metabolites were mainly excreted in urine. The main biotransformation products in plasma and urine were tentatively identified by cochromatography as dinor- and tetranoriloprost and their glucuronides. ADP-induced platelet aggregation was reduced by 60% during the i.v. infusion and 15 min after oral administration of 0.48 microgram/kg. Heart rate and blood pressure were virtually unaffected. Common side-effects were facial flush, headache and nausea.
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D011464:Epoprostenol / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D005483:Flushing / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D016285:Iloprost; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D013329:Structure-Activity Relationship; D014316:Tritium; D014664:Vasodilation / Q000187:drug effects
D014316:Tritium; D011464:Epoprostenol; D016285:Iloprost