Metabolic Fate of Nifedipine Suppository in Rats.

Abstract

14C-Nifedipine suppository was administered intrarectally (i.r.) in rat, in order to investigate its absorption, distribution, metabolism and excretion, comparing with the data after intravenous (i.v.) or oral (p.o.) administration of 14C nifedipine solution. Also the metabolic fate was investigated after daily dosing of 14C-nifedipine suppository. 1. After i.v. administration, the level of radioactivity in the blood decreased biphasically, with the corresponding half-lives of 1. Ohr and 38.5hr, respectively. The maximum concentration of radioactivity in the blood at 45min after i.r. administration was higher than that observed after p.o. application. 2. The excretion ratio of radioactivity in the urine and feces was similar among those 96hr after i.r., i.v. and p. o. administration ; 51 ?? 53 and 46 ?? 41% of dose in the urine and feces, respectively. 3. The distrubution of radioactivity in tissues after i.r. administration was similar to that of p.o. administration except that in gastro-intestinal tract. At 45min after i.r. administration, the tissue levels of radioactivity were higher in the liver, kidney and plasma than blood, and very low in brain. 4. Metabolites in the plasma and urine after 3 different administration routes were simil ar. Unchanged 14C-Nifedipine was found in plasma at the early period after administration, but not in urine. 5. During the repeated intrarectal administration, the level of radioactivity in the blood at 24hr after daily dosing continued to increase till the 7th day, then reached to the plateau. The excretion rates of radioactivity in the urine and feces were nearly constant during the period of repeats, and were similar to those after a single administration. The tissue levels of radioactivity appeared not to be accumulated in the tissues.