[Studies on the pharmacokinetics of BMY-28100 (I)].

The pharmacokinetics of BMY-28100 have been studied in rats and monkeys upon oral administration of 14C-BMY-28100. 1. In rats administered with BMY-28100 at a single oral dose of 20 mg/kg, the peak blood level of the drug was 6.30 micrograms equiv./ml at 1 hour after administration. Blood levels declined biphasically, thereafter. The AUC value was 37.0 micrograms equiv..hr/ml, and was 97% of that observed after intravenous administration. This suggests that BMY-28100 is absorbed at a high absorption rate from the gastro-intestinal tract. 2. In monkeys administered with a single oral dose of 20 mg/kg, the peak blood level was 4.26 micrograms equiv./ml at 3 hours after administration. Thereafter, blood levels declined biphasically as did in rats. The AUC was 38.9 micrograms equiv..hr/ml, which is similar to that observed in rats. 3. Urinary and fecal excretion after 20 mg/kg oral administration were 60.9% and 38.1%, respectively, in rats, and 40.3% and 51.2%, respectively, in monkeys. 4. Although absorption from gastro-intestinal tract was delayed by food intake, this did not affect the total amount absorbed in rats. 5. The absorption rates were similar in rats administered with 20 and 60 mg/kg, while a lower rate was obtained with 200 mg/kg. 6. In rats, biliary excretion was 28.5% of dose administered. Thirty-nine percent of the biliary radioactivity was reabsorbed from the intestinal tract. 7. No differences between sexes were observed in absorption and excretion in rats administered with the drug at 20 mg/kg orally. 8. In rats administered with 20 mg/kg, the radioactivity distributed rapidly to the whole body. High levels of radioactivity were found in gastro-intestinal tract, kidney, urinary bladder, aorta and liver. The radioactivity was removed rapidly from the tissues. Autoradiograms of the whole body were consistent with the measured tissue distribution. Relatively high levels of radioactivity were found in aorta, fascia, and ligament at 0.5, 1, 6, and 24 hours. 9. In vivo protein binding, which increased with time after administration, was 56.8 to 73.5% in rat and 36.3 to 58.6% in monkey. The in vitro protein binding at 0.4 to 50 micrograms/ml of drug concentration was 50.0 to 54.7% in rat, 32.3 to 35.0% in monkey, and 33.4 to 36.3% in human. 10. A stability test of 14C-BMY-28100 in plasma solution showed that the drug decomposed gradually into relatively polar compound(s). At 8 and 24 hours, the proportions of unchanged 14C-BMY-28100 were 53.2% and 5.9%, respectively.