Pharmacokinetics of PN 200-110 (isradipine), a new calcium antagonist, after oral administration in man.

The pharmacokinetics of PN 200-110 (isradipine), a new calcium channel blocking agent, have been studied in 18 normal male volunteers who received orally a single 5-mg dose, a single 20-mg dose, or repeated administration of 5 mg every 8 h for 13 doses of [14C]PN 200-110. PN 200-110 was rapidly and almost completely (90-95%) absorbed from the gastrointestinal tract, although the estimated bioavailability was only 17% due to extensive first-pass metabolism. The pharmacokinetics of PN 200-110 appeared to be linear in the 5 to 20-mg dose range, as indicated by the dose-proportional blood levels of total radioactivity as well as the parent drug. Absorbed PN 200-110 was completely metabolized prior to excretion. The recovery of radioactivity after both the 5 and the 20-mg dose was virtually complete within the experimental period, with a renal:fecal excretion ratio of ca. 70:30. Repeated administration of [14C]PN 200-110 showed no change in pharmacokinetic characteristics. During the 5 mg thrice daily regimen, steady-state blood levels of parent drug were reached in 2 days while those of total radioactivity were reached in approximately 4 days. PN 200-110 and total radioactivity accumulated in blood by a factor of 2.1 and 3.4, respectively, indicating effective half-lives of 8.8 h and 16 h. The oral administration of [14C]PN 200-110 prescribed in the present study was safe and well tolerated.