Pharmacokinetics of Nimodipine. II. Communication: distribution, elimination and placental transfer in rats following single and multiple doses of [14C]nimodipine.

(+/-)Isopropyl-2-methoxyethyl-1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl)-3,5-pyridinedicarboxylate (nimodipine, Bay e 9736, Nimotop) is a calcium antagonist from the 1,4-dihydropBridine group which influences the cerebral blood flow. The active substance labelled with carbon-14 was administered orally or intravenously to rats at doses ranging from 1 to 10 mg/kg. The objective of the study was to determine the course of the distribution of total radioactivity among organs and tissues, to investigate the extent and kinetics of diaplacental transfer and to study the influence of continuous treatment over three weeks on concentrations and elimination kinetics in organs and tissues. The radioactivity concentration was determined qualitatively by whole-body autoradiography or quantitatively after autopsy. Following intravenous administration the radioactivity of [14C]nimodipine is distributed rapidly and uniformly. Later, and also after oral administration, the distribution pattern is strongly differentiated with high concentrations in the liver, kidneys and fat and low concentrations in the brain and testes and subsequently in the plasma. Within one day the concentration in the animal excluding the gastrointestinal tract falls by a factor of 25 and a slow elimination phase then ensues. Only a little of the radioactivity of nimodipine passes through the placental barrier. The distribution patterns and excretion routes detected in the foetus are essentially the same. The radioactivity concentration in the foetus was a factor of 8-15 lower than in the dam.(ABSTRACT TRUNCATED AT 250 WORDS)