Tse F L, Jaffe J M
Eur J Clin Pharmacol. 1987;32(4):361-5. doi: 10.1007/BF00543970.
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.
新型钙通道阻滞剂PN 200-110（伊拉地平）的药代动力学已在18名正常男性志愿者中进行了研究，这些志愿者口服了单次5毫克剂量、单次20毫克剂量，或每8小时重复给药5毫克，共13剂的[14C]PN 200-110。PN 200-110从胃肠道迅速吸收且几乎完全（90-95%）吸收，尽管由于广泛的首过代谢，估计生物利用度仅为17%。PN 200-110的药代动力学在5至20毫克剂量范围内似乎呈线性，总放射性以及母体药物的血药浓度与剂量成比例即可表明。吸收的PN 200-110在排泄前完全代谢。5毫克和20毫克剂量后的放射性回收率在实验期内几乎完全，肾排泄与粪便排泄之比约为70:30。重复给予[14C]PN 200-110后，药代动力学特征无变化。在每日三次5毫克的给药方案中，母体药物在2天内达到稳态血药浓度，而总放射性在约4天内达到。PN 200-110和总放射性在血液中的蓄积系数分别为2.1和3.4，表明有效半衰期分别为8.8小时和16小时。本研究中规定的口服[14C]PN 200-110是安全的且耐受性良好。
