Bagli M, Rao M L, Höflich G, Kasper S, Langer M, Barlage U, Beneke M, Süverkrüp R, Möller H J
Psychiatrische Klinik und Poliklinik, Rheinischen Friedrich-Wilhelms-Universität, Bonn, Germany.
Arzneimittelforschung. 1996 Mar;46(3):247-50.
The absolute and relative bioavailability of chlorprothixene (CAS 113-59-7, Truxal) was studied in eight healthy male volunteers with three different formulations: solution, suspension and coated tablet. An intravenous infusion and an oral aqueous solution served as references. Single doses of 100 mg were administered in a randomized complete-block design with washout periods of two weeks. Serum concentrations of chlorprothixene were assayed using a high-performance liquid chromatographic method with electrochemical detection. After a 1-h infusion period the maximum serum concentration (Cmax) of chlorprothixene was 430 +/- 81 ng/ml (mean +/- S.D.) and subsequently decreased with a terminal elimination half-life (t1/2) of 25.8 +/- 13.6 h. The total serum clearance (Cl) and the apparent volume of distribution at steady state (Vss) were 867 +/- 167 ml/min and 1035 +/- 356 l, respectively. The profiles of the chlorprothixene serum concentration vs. time and the resulting pharmacokinetic parameters were similar for all orally administered formulations. The absolute oral bioavailability of 17% of the solution indicated a marked presystemic metabolism. The bioavailability of chlorprothixene relative to the oral solution was 56.4% with the coated tablet and 67.7% with the suspension. All pharmacokinetic parameters showed wide inter-subject variations, partly attributable to the respective formulation.
在8名健康男性志愿者中，使用三种不同剂型（溶液剂、混悬剂和包衣片）研究了氯丙硫蒽（CAS 113 - 59 - 7，Truxal）的绝对生物利用度和相对生物利用度。静脉输注和口服水溶液作为对照。采用随机完全区组设计，给予单剂量100 mg，洗脱期为两周。采用高效液相色谱电化学检测法测定血清中氯丙硫蒽的浓度。在1小时输注期后，氯丙硫蒽的最大血清浓度（Cmax）为430±81 ng/ml（均值±标准差），随后下降，终末消除半衰期（t1/2）为25.8±13.6小时。总血清清除率（Cl）和稳态表观分布容积（Vss）分别为867±167 ml/min和1035±356 l。所有口服剂型的氯丙硫蒽血清浓度-时间曲线和由此得出的药代动力学参数相似。溶液剂17%的绝对口服生物利用度表明存在明显的首过代谢。相对于口服溶液，氯丙硫蒽包衣片的生物利用度为56.4%，混悬剂为67.7%。所有药代动力学参数在个体间均表现出较大差异，部分归因于各自的剂型。
