注射用比阿培南的健康人体药动学研究

Pharmacokinetics of Biapenem for Injection in Healthy Volunteers

目的研究中国健康受试者单剂量静滴比阿培南后的药动学过程。方法30名健康受试者（男性15名，女性15名）按体重指数和性别随机分为3组，单剂量（0．15，0．3，0．6g）静滴比阿培南后，于不同时间分别从受试者肘静脉取血3mL，离心分离血浆，采用高效液相色谱法测定血浆中比阿培南浓度。用DAS（ver2．0．1）药动学软件进行房室模型判断并计算药动学参数。结果比阿培南的体内经时过程符合二房室模型，静滴低、中、高3个剂量比阿培南后的t1/2分别为（1．08±0．21），（1．04±0．09）和（1．12±0．08）h；ρmax分别为（8．02±0．94），（17．84±4．32）和（35．77±5．86）mg·L^-1；AUC0．6h分别为（13．05±1．89），（26．33±4．93）和（52．02±8．55）mg·h·L^-1ρmax和AUC0-6h与给药剂量呈正相关，回归方程分别为P～=0．0614X-0．9505，r=0．9436（P〈0．001）和AUC0—6h=0．0865X-0．2090，r=0．9467（P〈0．001）。结论健康人单剂量静滴0．15，0．3和0．6g比阿培南后，体内药动学呈二房室模型，比阿培南在0．15～0．6g内药物呈一级消除动力学，ρmax和AUC与给药剂量线性相关；男、女性受试者静滴注射用比阿培南后的体内药动学过程无明显差异。

OBJECTIVE To study the pharmacokinetics of biapenem in healthy volunteers. METHODS 30 Healthy volunteers （15 male, 15 female） were randomly divided into three pools, and was administered a single dose （0.15, 0.3, 0.6 g, iv） of biapenem by intravenous drip. Blood samples were collected from elbow vein at certain sampling times. Biapenem in plasma was determined by HPLC method, and the pharmacokinetic parameters were calculated by DAS software. RESULTS The plasma concentration-time curves of biapenem were fitted to a two-compartment model. The main pharmacokinetic parameters of a single dose （0.15, 0.3, 0.6 g, iv） were as follows., t1/2 （1.08±0.21）, （1.04±0.09） and （1.12±0.08） h; ρmax （8.02±0.94）, （17.84±4.32） and （35.77± 5.86）mg＇L-l; AUC0-6h （13.05±1.89）, （26.33 ±4.93） and （52.02 ± 8.55） mg.h.L^-1; the linear regressive equation was ρmax=0.061 4X-0.950 5, r= 0.943 6 （P〈0.001） andAUC0-6h=0.086 5X-0.209 0, r=0.946 7 （P〈0.001） between ρmax. AUC0-6h and biapenem doses. CONCLUSION The plasma concentration-time curves of biapenem were fitted to a two-compartment model with first order elimination after a single dose ofbiapenem （0.15, 0.3, 0.6 g, iv）, and the increases ofρmax and AUC were directly in positive correlation with that of biapenem doses. There was no significant difference in the pharmacokinetic parameters between female and male subjects.