van Harten J, van Brummelen P, Ooms P, Danhof M, Blauw G J, Breimer D D
Leiden University, Division of Pharmacology, The Netherlands.
J Clin Pharmacol. 1989 Aug;29(8):714-21. doi: 10.1002/j.1552-4604.1989.tb03405.x.
We investigated whether the effect of nisoldipine on liver blood flow depends on its route of administration. Ten healthy subjects took nisoldipine I.V. (infusion) and orally (without and with sotalol pretreatment). Pharmacokinetics of nisoldipine was assessed and liver blood flow (ICG clearance) was measured before dosing and at the end of the infusion or during absorption. During I.V. infusion the ICG plasma clearance increased by only 14%, whereas the increase was 60% during absorption of nisoldipine. Nisoldipine increases liver blood flow considerably only during the absorption phase. A positive correlation was found between the increase in liver blood flow during absorption and the systemic availability of nisoldipine, suggesting that the differences in liver blood flow response to nisoldipine substantially contribute to the variability in pharmacokinetics of the drug.
我们研究了尼索地平对肝血流量的影响是否取决于其给药途径。10名健康受试者静脉注射（输注）和口服尼索地平（未用和先用索他洛尔预处理）。评估尼索地平的药代动力学，并在给药前以及输注结束时或吸收期间测量肝血流量（吲哚菁绿清除率）。静脉输注期间，吲哚菁绿血浆清除率仅增加14%，而在尼索地平吸收期间增加了60%。尼索地平仅在吸收阶段显著增加肝血流量。吸收期间肝血流量的增加与尼索地平的全身可用性之间存在正相关，这表明对尼索地平肝血流量反应的差异在很大程度上导致了该药物药代动力学的变异性。
