Single daily dosing of gentamicin: pharmacokinetic comparison of two dosing methodologies for postpartum endometritis.

OBJECTIVE

We compared the pharmacokinetics of two methods for dosing gentamicin for the treatment of postpartum endometritis with the goal of achieving adequate peak serum concentrations (>12 mg/L) and prolonged trough levels below 2 mg/L.

METHODS

Group-I subjects (n = 5) received intravenous gentamicin, 5 mg/kg per total body weight over 60 min., with a maximum dose of 500 mg. Group-II subjects (n = 17) were dosed intravenously according to the following formula: Dose = desired peak concentration (fixed at 14 mg/L) * (volume of distribution, i.e., 0.35 L/kg) * adjusted body weight (in kilograms). Serum gentamicin levels were obtained 1 hr. and 8-12 hr. after infusion of the second dose. Pharmacokinetic parameters for the subjects in each group were calculated according to standard formulas.

RESULTS

Subjects in Group I had significantly higher doses and peak drug concentrations (P < 0.01), while in Group II, 76% of patients had peak levels less than desired (<12 mg/L). Both groups maintained trough levels of <2 mg/L in excess of 12 hr.

CONCLUSIONS

Changing to the adjusted body weight formula for Group I, while maintaining a dose between 4 and 5 mg/kg, would reduce excessive peak concentrations. Using a calculated volume of distribution of 0.4 L/kg in Group II would improve peak serum concentrations to the desired levels. Both dosing regimens ensure adequate aminoglycoside pharmacokinetic parameters and avoid the need for monitoring serial serum drug concentrations, provided the expected clinical response is also achieved. While the first dosing formula is simpler to calculate, the second dosing formula allows for more individualized dosing considerations.