Institute of Clinical Pharmacology, West China Hospital, Sichuan University, Chengdu, China.
J Clin Pharm Ther. 2010 Feb;35(1):113-9. doi: 10.1111/j.1365-2710.2009.01075.x.
To investigate the safety and pharmacokinetics of bromotetrandrine (BrTet, W198), a novel inhibitor of P-glycoprotein (P-gp), after single-dose i.v. infusion in healthy Chinese volunteers.
We conducted a randomized, dose-escalating, phase I clinical study for that purpose. Thirty healthy subjects received BrTet at the doses of 10, 20 or 30 mg/m(2) by i.v. infusion. Plasma and urine concentrations of bromotetrandrine were determined by using a liquid chromatography-tandem mass spectrometric (LC/MS/MS) method. AUC was calculated by the trapezoidal rule extrapolation method. C(max), T(max), t(1/2alpha), t(1/2beta), Cl and V(d) were compiled from the plasma concentration-time data.
Bromotetrandrine was generally well tolerated at all doses. No serious or severe adverse events were found in the study. The pharmacokinetic parameters of BrTet after single i.v. infusion doses of BrTet 10, 20 and 30 mg/m(2) were as follows: T(max) were 1.5 h in three groups, C(max) were 24.79, 39.59 and 64.31 microg/L, t(1/2alpha) were 0.37, 0.29 and 0.30 h, t(1/2beta) were 62.88, 56.45 and 52.20 h. AUC(0-194h) were 345.83, 688.15 and 1096.28 microg h/L, Cl were 23.68, 25.69 and 25.66 L h/m(2), V(d) were 157.73,156.96 and 140.73 L/m(2). In urine, the total eliminate rate of originate compound was 0.61 +/- 0.19%.
This study suggested that bromotetrandrine was well tolerated in healthy volunteers within the dose range evaluated. The pharmacokinetics parameters of bromotetrandrine indicated that the compound was rapidly distributed and accumulated in the tissues, and slowly cleared from plasma, which supported the use of BrTet for a once or twice dosing per chemotherapy cycle.
研究新型 P 糖蛋白（P-gp）抑制剂溴夫定（BrTet，W198）在健康中国志愿者单次静脉输注后的安全性和药代动力学。
为此目的，我们进行了一项随机、剂量递增、I 期临床研究。30 名健康受试者按静脉输注 10、20 或 30 mg/m2 的剂量接受 BrTet。采用液相色谱-串联质谱（LC/MS/MS）法测定溴夫定的血浆和尿液浓度。采用梯形规则外推法计算 AUC。C（max）、T（max）、t1/2alpha、t1/2beta、Cl 和 V（d）由血浆浓度-时间数据编译而成。
BrTet 在所有剂量下均耐受良好。研究中未发现严重或严重不良事件。BrTet 单次静脉滴注剂量为 10、20 和 30 mg/m2 时，BrTet 的药代动力学参数如下：T（max）在三组中均为 1.5 h，C（max）分别为 24.79、39.59 和 64.31 μg/L，t1/2alpha 分别为 0.37、0.29 和 0.30 h，t1/2beta 分别为 62.88、56.45 和 52.20 h。AUC（0-194h）分别为 345.83、688.15 和 1096.28μg h/L，Cl 分别为 23.68、25.69 和 25.66 L h/m2，V（d）分别为 157.73、156.96 和 140.73 L/m2。在尿液中，原始化合物的总消除率为 0.61±0.19%。
本研究表明，溴夫定在评估剂量范围内的健康志愿者中耐受良好。溴夫定的药代动力学参数表明，该化合物在组织中快速分布和积累，从血浆中缓慢清除，这支持 BrTet 每化疗周期使用一次或两次。
