Munar M Y, Lawson L A, Samuels P, Gibson G A
College of Pharmacy, Oregon State University, Oregon Health Sciences University Hospital, Portland.
DICP. 1991 Dec;25(12):1306-9. doi: 10.1177/106002809102501203.
The pharmacokinetics of gentamicin in postpartum women with endomyometritis were characterized and models for predicting patient pharmacokinetic parameters were developed using multiple regression analysis. Fifty-one women 13-34 years of age received gentamicin in combination with either ampicillin or clindamycin to treat endomyometritis. Forty-three women delivered by cesarean section and 8 women had vaginal deliveries. Gentamicin serum concentrations were determined at steady-state to compute the elimination rate constant (Kc), half-life (t1/2), apparent volume of distribution (Vd), and total body clearance (Cl). Gentamicin dosages were individualized using a one-compartment intermittent infusion model to achieve steady-state peak and trough concentrations of 6.5 and less than 2 micrograms/mL, respectively. The mean gentamicin t1/2 was 2.8 +/- 0.9 h; the mean apparent Vd was 21 +/- 8 L; and the mean total body Cl was 89.5 +/- 31.7 mL/min. Multiple regression analysis revealed that total body weight (TBW) was the best predictor for the apparent Vd, described by the equation Vd = 0.146 TBW + 8.153 (r = 0.56, p = 0.00005). Total body weight and creatinine clearance (Clcr) were included as predictors for total body Cl, described by the equation Cl = 0.264 TBW + 0.337 Clcr + 3.416 (r = 0.68, p = 0.00005). Age and serum creatinine (SCr) were included in the models for the Ke, described by the equation Ke = -3.770 x 10(-3) age -0.115 SCr + 0.449 (r = 0.42, p less than 0.004). Additional patient factors need to be identified to explain the variance in these pharmacokinetic parameters.
对患有子宫内膜炎的产后女性庆大霉素的药代动力学特征进行了研究，并采用多元回归分析建立了预测患者药代动力学参数的模型。51名年龄在13至34岁之间的女性接受了庆大霉素联合氨苄西林或克林霉素治疗子宫内膜炎。43名女性通过剖宫产分娩，8名女性经阴道分娩。在稳态时测定庆大霉素血清浓度，以计算消除速率常数（Kc）、半衰期（t1/2）、表观分布容积（Vd）和总体清除率（Cl）。使用单室间歇输注模型对庆大霉素剂量进行个体化调整，以使稳态峰浓度和谷浓度分别达到6.5和低于2微克/毫升。庆大霉素的平均t1/2为2.8±0.9小时；平均表观Vd为21±8升；平均总体Cl为89.5±31.7毫升/分钟。多元回归分析显示，总体重（TBW）是表观Vd的最佳预测指标，其方程为Vd = 0.146 TBW + 8.153（r = 0.56，p = 0.00005）。总体重和肌酐清除率（Clcr）被纳入总体Cl的预测指标，其方程为Cl = 0.264 TBW + 0.337 Clcr + 3.416（r = 0.68，p = 0.00005）。年龄和血清肌酐（SCr）被纳入Ke的模型，其方程为Ke = -3.770×10⁻³年龄 - 0.115 SCr + 0.449（r = 0.42，p < 0.004）。需要确定其他患者因素来解释这些药代动力学参数的差异。
