正常人及缺血性脑血管病病人的盐酸川芎嗪临床药代动力学研究

THE CLINICAL PHARMACOKINETIC STUDIES OF TETRAMETHYLPYRAZINE HYDROCHLORIDE IN NORMAL VOLUNTEERS AND PATIENTS WITH ACUTE CEREBRAL ISCHEMIA DISEASE (CID)

正常志愿者12人一次肌注及急性缺血性脑血管病患者7人首次静脉点滴盐酸川芎嗪(TMPH)的药代动力学研究表明,肌注TMPH40mg后,0.25-0.5h达吸收高峰,药物分布及消除迅速。静脉滴注80mg TMPH 3-4h,其平均峰浓度为407.49±84.68ng/ml,停药后血药浓度在3-8h后已检测不到。分布与消除规律同肌注。采用平衡透析法测得川芎嗪人血浆蛋白结合率为44.3±2.9%,为中等程度血浆蛋白结合药物。

Tetramethylpyrazine(TMPZ). a pure alkaloid isolated fromtraditional Chinese herb, Ligustium Wellichii Franchet, has been widelyused in the treatment of patients with cerebral ischemia disease in ourcountry since 70 's. In this paper, the clinical pharmacokinetics of tetr-amethylpyrazine in normal volunteers (im) and patients with CID (iv. inf)and the plasma protein binding of TMPZ in human and rabbits were stu-died. The results showed that the concentration-time curves mainly fittedto two compartment open model and first order kinetic elimination afterintramuscularly administration of a single dose of 40mg tetramethylpyra-zine hydrochloride (TMPH) in 12 normal subjects and after a initial in-travenous infusion of 80mg of TMPH dissolved in 500ml 5 % glucose solu-tion in 7 patients with CID. The pharmacokinetic parameters calculated wi-th MCPKP program and IBM computer were Ka: 5.0381± 1. 1136/h; t1/2 ka:0. 14±0 .03h; tp: 0.50±0. 11h; Vd: 64. 89± 22. 74 1 (im) and 66.60 ±20. 901(iv.inf): t1/2 β: 2. 10±0.03h (im) and 1 .61±0.42h (iv.inf); Kel: 0.6782±0. 2502/h (im) and 1. 2293±0. 61 70/h (iv .inf); Clp: 21. 86±5.23 1/h(im) and29. 36± 8.38 1 /h (iv. inf) respectively. Thus, the results indicated thatTMPH was rapidly absorbed (im), distributed and eliminated in the body. Using method of equilibrium dialysis, the protein binding of TMPZwas 44.:10 ±2. 90% in human plasma and 46. 80±2. 30% in rabbits. The re-sults indicated the TMPZ was a moderate plasma protein binding drug andthere was no relationship between the level of plasma protein binding anddrug concentration in the range of 0. 125-4.0μg/ml of TMPZ.