PHARMACOKINETICS OF AMPICILLIN AND SULBACTAM IN PREGNANCY

OBJECTIVE: This study evaluated the effects pregnancy had on pharmacokinetic parameters of ampicillin and sulbactam. STUDY DESIGN: Twenty-two women undergoing cesarean section for obstetric indications were randomly assigned to receive a single intraoperative dose of either 1 gm of ampicillin intravenously or 1 gm of ampicillin plus 0.5 gm of sulbactam intravenously after umbilical cord clamping. Blood was drawn from an indwelling intravenous catheter at 15, 30, 45, 60, 120, 240, and 360 minutes after infusion of the antibiotic for determination of serum ampicillin and/or sulbactam levels. Pharmacokinetic parameters were determined by fitting data (serum concentrations versus time) to a single-compartment model that provided elimination rate constants, beta-intercept (calculated concentration at 0 minutes), area under the time-versus-concentration curve, half-life of the drug, total body clearance, and volume of distribution. After the examination 6 weeks post partum, each subject was given an additional dose of the drug she had received during cesarean section, and a second pharmacokinetic study was performed and compared with the previous results. RESULTS: Pregnancy significantly increased the elimination rate constant, decreased the area under the drug-versus-time curve, shortened the serum half-life, and increased the total body clearance in comparison with these parameters in the nonpregnant state for ampicillin. Sulbactam kinetics were similarly affected, although these changes failed to attain statistical significance. CONCLUSION: Because pregnancy is associated with more rapid elimination of beta-lactam drugs, physicians treating infections in pregnant or newly parturient women should consider using shorter intervals between antibiotic doses when a range of dosage intervals is under consideration.