Chandler M H, Clifton G D, Lettieri J T, Mazzu A L, Allington D R, Thieneman A C, Foster T S, Harrison M R
Drug Product Evaluation Unit, University of Kentucky Medical Center, Lexington.
J Clin Pharmacol. 1992 Jun;32(6):571-5. doi: 10.1177/009127009203200614.
This randomized double-blind parallel group study characterized the pharmacokinetics of the calcium channel antagonist, nisoldipine (core-coat tablets), administered once daily for 7 days in doses of 5 mg (n = 12), 10 mg (n = 13), 20 mg (n = 12), and 30 mg (n = 11) to patients with mild to moderate hypertension. Serial blood samples were obtained from 0 to 24 hours and from 0 to 48 hours after nisoldipine administration on days 1 and 7, respectively. Nisoldipine plasma concentrations were determined by gas chromatography with electron capture detection. No statistically significant difference was found in dose-normalized area under the curve between the four groups. Area under the curve (standardized to body weight) correlated to dose (r = .74, P less than .05). No significant difference existed in oral clearance (L/h/kg) when analyzed for equivalence across the four doses: 8.21 +/- 3.47 (5 mg), 11.84 +/- 13.85 (10 mg), 11.48 +/- 7.49 (20 mg), and 10.36 +/- 5.49 (30 mg). The present investigation characterizes the pharmacokinetics of nisoldipine core-coat tablets in hypertensive patients and demonstrates the dose proportionality or linearity of nisoldipine plasma concentrations and area under the curve, measured over a dose range of 5 to 30 mg.
这项随机双盲平行组研究对钙通道拮抗剂尼索地平（双层包衣片）的药代动力学进行了表征，该药物以5毫克（n = 12）、10毫克（n = 13）、20毫克（n = 12）和30毫克（n = 11）的剂量每日给药一次，持续7天，用于轻度至中度高血压患者。分别在第1天和第7天尼索地平给药后0至24小时以及0至48小时采集系列血样。尼索地平血浆浓度通过带有电子捕获检测的气相色谱法测定。四组之间在剂量标准化曲线下面积方面未发现统计学上的显著差异。曲线下面积（按体重标准化）与剂量相关（r = 0.74，P小于0.05）。对四种剂量进行等效性分析时，口服清除率（升/小时/千克）无显著差异：8.21±3.47（5毫克）、11.84±13.85（10毫克）、11.48±7.49（20毫克）和10.36±5.49（30毫克）。本研究对尼索地平双层包衣片在高血压患者中的药代动力学进行了表征，并证明了在5至30毫克的剂量范围内，尼索地平血浆浓度和曲线下面积的剂量比例性或线性关系。
