title: Pharmacokinetics of rolipram in the rhesus and cynomolgus monkeys, the rat and the rabbit. Studies on species differences.
abstract: 1. The pharmacokinetics of rolipram were studied in rat, rabbit, rhesus monkey and cynomolgus monkey using 14C- or 3H-labelled rolipram and a radioimmunoassay for measurement of unchanged drug. 2. Rolipram was rapidly and completely absorbed after oral doses of up to 50 mg/kg. Bioavailability was 0.1% in rhesus monkey, 3.7% in cynomolgus monkey, 3.6% in rabbit, 35% in rat, and 75% in man. 3. Rolipram was able to pass the blood-brain barrier achieving concentrations in brain twice those in plasma. 4. Plasma levels of the unchanged drug declined with a similar half-life of 1-3 h in all species investigated. In the rat, there were indications for a different clearance of the two rolipram enantiomers. 5. Labelled rolipram was excreted rapidly and completely. The main route of elimination was via the urine.
authors.affiliation: Department of Pharmacokinetics, Schering AG, Berlin, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Krause
authors.forename: G
authors.initials: G
authors.lastname: Kühne
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000187:drug effects; D005260:Female; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D011760:Pyrrolidinones / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D020889:Rolipram; D013045:Species Specificity; D013237:Stereoisomerism
chemical_list: D000928:Antidepressive Agents; D011760:Pyrrolidinones; D020889:Rolipram