Lo C F, Chen C M
School of Pharmacy, Taipei Medical College, Taiwan.
Biopharm Drug Dispos. 1996 Dec;17(9):791-803. doi: 10.1002/(SICI)1099-081X(199612)17:9<791::AID-BDD993>3.0.CO;2-T.
The pharmacokinetics of higenamine were investigated in rabbits by IV bolus, PO route, and IV infusion. Plasma higenamine concentration declined rapidly in a biexponential pattern, with a terminal half-life of 22 min. The AUC increased proportionally with increasing dose, whereas the percentage of unchanged higenamine excreted from urine remained constant when dose was increased. The means of total body clearance, mean residence time, volume of distribution at steady state, and fraction of urinary excretion were 127.7 mL min-1 kg-1, 9.28 min, 1.44 kg-1, and 5.48%, respectively. The mean percentage of protein binding of higenamine in plasma was 54.8% at steady state after IV infusion. The results from post-infusion also confirmed that higenamine followed a two-compartment open model in animals. After oral administration, higenamine was rapidly absorbed to reach peak concentration within 10 min. Interestingly, the plasma concentration-time profiles revealed two distinguishable groups with different Cmax, extent of absorption, and urinary excretion. The average absolute bioavailabilities of higenamine calculated by AUCs and accumulated urinary excretion were 21.86 and 2.84% versus 20.19 and 5.50% for the two groups, respectively. Upon hydrolysis of urine samples with beta-glucuronidase, urinary concentrations of higenamine were greatly enhanced in both groups.
通过静脉推注、口服给药和静脉输注的方式，在兔体内研究了去甲乌药碱的药代动力学。血浆去甲乌药碱浓度呈双指数模式迅速下降，终末半衰期为22分钟。曲线下面积（AUC）随剂量增加成比例增加，而当剂量增加时，从尿液中排泄的原形去甲乌药碱百分比保持恒定。总体清除率、平均驻留时间、稳态分布容积和尿排泄分数的平均值分别为127.7 mL·min⁻¹·kg⁻¹、9.28分钟、1.44 kg⁻¹和5.48%。静脉输注后稳态时，血浆中去甲乌药碱的平均蛋白结合率为54.8%。输注后结果也证实，去甲乌药碱在动物体内符合二室开放模型。口服给药后，去甲乌药碱迅速吸收，在10分钟内达到峰值浓度。有趣的是，血浆浓度-时间曲线显示出两组具有不同的最大血药浓度（Cmax）、吸收程度和尿排泄的可区分群体。通过AUC和累积尿排泄计算的去甲乌药碱平均绝对生物利用度，两组分别为21.86%和2.84%，以及20.19%和5.50%。用β-葡萄糖醛酸酶水解尿样后，两组中去甲乌药碱尿浓度均大幅提高。
