Foster T S, Hamann S R, Richards V R, Bryant P J, Graves D A, McAllister R G
J Clin Pharmacol. 1983 Apr;23(4):161-70. doi: 10.1002/j.1552-4604.1983.tb02720.x.
Nifedipine kinetics have not been described in clinically relevant detail because of difficulties in formulating a stable preparation for intravenous use and lack of a specific and sensitive assay for plasma nifedipine. We recently developed a gas-chromatographic method and determined conditions in which nifedipine could be protected from photodegradation. Therefore, we evaluated the kinetics and bioavailability of nifedipine in 12 normal subjects after single intravenous (1 mg/5 min) and oral (10 mg) doses. After intravenous dosing, the drug was eliminated with a half-time of 1.77 +/- 0.25 hour, and total clearance was calculated at 0.62 +/- 0.09 liter/kg/hr. With oral drug administration, the elimination half-time was twice as long for the group; but within these subjects, marked variability in the rate of appearance of the drug in plasma was observed, giving profiles consistent with fast and slow absorption. In the latter group, peak plasma drug concentrations were only one third the level seen in those exhibiting a faster absorption profile, although the extent of drug absorption (as derived from areas under the plasma level-time curves) did not vary. Bioavailability was 0.45 +/- 0.08. Untoward effects resulting from the drug's pharmaco-subjects after intravenous administration (flushing).
由于难以制备稳定的静脉用制剂以及缺乏针对血浆硝苯地平的特异性灵敏检测方法，硝苯地平的动力学尚未得到临床相关的详细描述。我们最近开发了一种气相色谱法，并确定了能保护硝苯地平免受光降解的条件。因此，我们评估了12名正常受试者单次静脉注射（1毫克/5分钟）和口服（10毫克）剂量后硝苯地平的动力学和生物利用度。静脉给药后，药物消除半衰期为1.77±0.25小时，总清除率计算为0.62±0.09升/千克/小时。口服给药时，该组的消除半衰期延长了一倍；但在这些受试者中，观察到药物在血浆中出现的速率存在显著差异，其曲线与快速和缓慢吸收一致。在后一组中，血浆药物峰浓度仅为吸收较快组的三分之一，尽管药物吸收程度（由血浆水平-时间曲线下面积得出）并无变化。生物利用度为0.45±0.08。静脉给药后，药物的药理学效应导致受试者出现潮红等不良反应。
