Gentamicin Pharmacokinetics in Postpartum Women with Endomyometritis

Abstract

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 (K_e), half-life (t1/2), apparent volume of distribution (V_d), 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 <2 μg/mL, respectively. The mean gentamicin t1/2 was 2.8 ± 0.9 h; the mean apparent V_d 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 V_d, described by the equation V_d = 0.146 TBW + 8.153 (r=0.56, p=0.00005). Total body weight and creatinine clearance (Cl_cr) were included as predictors for total body Cl, described by the equation Cl = 0.264 TBW + 0.337 Cl_cr + 3.416 (r=0.68, p=0.00005). Age and serum creatinine (SCr) were included in the models for the K_e, described by the equation K_e = −3.770 · 10⁻³ age — 0.115 SCr + 0.449 (r=0.42, p<0.004). Additional patient factors need to be identified to explain the variance in these pharmacokinetic parameters.