溴泰君(W198)在大鼠和比格狗体内的药代动力学

Pharmacokinetics of bromotetrandrin (W198) in rats and beagle dogs

目的 研究溴泰君 (W 198)在大鼠和比格狗的药代动力学。方法 采用HPLC紫外检测方法测定大鼠及比格狗注射W 198后血清药物浓度。结果 大鼠ivW19810 ,2 0和 40mg·kg- 13个剂量的T1 2 β分别为 6 60 ,7 3 6和6 77h ,AUC0 - 2 4h分别为 3 797,7 3 71和 15 192mg·h·L- 1,Vd 分别为 7 14 ,4 3 3和 4 13L·kg- 1,CL分别为 2 83 ,2 60和2 71L·(kg·h) - 1。大鼠imW 1982 0mg·kg - 1后T1 2 β为 11 61h ,AUC0 - 2 4h 为 4 191mg·h·L - 1,im的生物利用度为56 9%。比格狗ivW1985mg·kg- 1,T1 2 β为 11 72h ,AUC0 - 2 4h 为 12 646mg·h·L- 1,Vd 为 0 70L·kg- 1,CL为 0 46L·(kg·h) - 1。W198与人血浆蛋白的结合率平均为 78 0 %。结论 W198im的T1 2 β比iv的略长 ,其生物利用度为56 9%。在 10～ 40mg·kg-

AimTo study the pharmacokinetics of bromotetrandrine (W198) in rats and beagle dogs. MethodsThe concentrations of W198 in serum were determined using HPLC method with UV de tection. ResultsThe pharmacokinetic parameters of W198 after single iv doses of W198 10, 20 and 40 mg·kg -1 in rats were as follows: T 1/2 β were 6 60, 7 3 6 and 6 77 h, AUC 0-24 h were 3 797 , 7 371 and 15 192 mg ·h·L -1 , V d were 7 14, 4 33 and 4 13 L·kg -1 , CL wer e 2 83, 2 60 and 2 71 L·(kg·h) -1 , respectively. The T 1/2 β and AUC 0-24 h of W198 after single im dose of W198 20 mg·kg -1 in rats were 11 61 h and 12 646 mg·h·L -1 . The im bioavail ability of W198 in rats was 56 9%. The T 1/2 β, AUC 0-24 h , V d and CL of W198 after single iv dose of W198 5 mg·kg -1 in beagle d ogs were 11 72 h, 12 646 mg·h·L -1 , 0 70 L·kg -1 and 0 46 L·(kg·h) -1 , respectively. The plasma protein binding ratio of W198 with human serum protein was 78 0%. ConclusionThe absorption of W198 in rats was of first order kinetics.