Pharmacokinetics of rolipram in the rhesus and cynomolgus monkeys, the rat and the rabbit. Studies on species differences.
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.
Krause
W
W
Department of Pharmacokinetics, Schering AG, Berlin, Germany.
Kühne
G
G
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
D000928:Antidepressive Agents; D011760:Pyrrolidinones; D020889:Rolipram