Fourtillan J B, Brisson A M, Couet W
CEMAF, Poitiers.
Therapie. 1993 Mar-Apr;48(2):115-8.
Pharmacokinetics of prazosin was investigated after single dose administrations of four different formulations, according to a randomized trial, to 24 young healthy volunteers: immediate release tablets (3 x 1 mg) used as reference (Treatment A), two new Gastro-Intestinal-Therapeutic-Systems (GITS) containing 2.5 mg (Treatment B) and 5 mg (Treatment C) of prazosin, and a traditional sustained release formulation (4 mg, treatment D). Relative bioavailability of prazosin administered as GITS was only 49.4 +/- 19.5% (B) and 45.5 +/- 18.7 (C) versus 73.8 +/- 13.9% (D) (area under the curve normalized at 3 mg dosing); but absorption was sustained and plasma concentrations were maintained at a virtually constant level for a time period close to 24 h. As a result, mean residence time (MRT) of prazosin was considerably increased after GITS administration: 21.6 +/- 1.0 h (B), 22.5 +/- 1.6 h (C) instead of 5.9 +/- 0.2 h for the reference formulation (A) and 10.8 +/- 0.8 h for the traditional sustained release formulation (D). Although extrapolation to multiple dosing situations is difficult, this study demonstrates the potential suitability of prazosin GITS for once daily administrations.
根据一项随机试验，对24名年轻健康志愿者单次服用四种不同剂型后，研究了哌唑嗪的药代动力学：速释片（3×1毫克）用作对照（治疗A），两种新型胃肠道治疗系统（GITS）分别含有2.5毫克（治疗B）和5毫克（治疗C）哌唑嗪，以及一种传统缓释制剂（4毫克，治疗D）。与传统缓释制剂（D）的73.8±13.9%（以3毫克给药剂量标准化后的曲线下面积）相比，以GITS形式给药的哌唑嗪的相对生物利用度仅为49.4±19.5%（B）和45.5±18.7%（C）；但吸收是持续的，血浆浓度在接近24小时的时间段内维持在几乎恒定的水平。结果，服用GITS后哌唑嗪的平均驻留时间（MRT）显著增加：（B组为21.6±1.0小时，C组为22.5±1.6小时），而对照制剂（A）为5.9±0.2小时，传统缓释制剂（D）为10.8±0.8小时。尽管很难外推到多剂量情况，但这项研究证明了哌唑嗪GITS每日一次给药的潜在适用性。
