Single-dose pharmacokinetics of intravenous ampicillin plus sulbactam in healthy elderly and young adult subjects

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Abstract
The pharmacokinetics of intravenous ampicillin and sulbactam, a β-lactamase inhibitor, were evaluated in two different age groups. Twelve healthy elderly subjects (age 65–93 years) and 12 healthy young adult subjects (age 20–35 years) received both a dose of ampicillin 1 g plus sulbactam 0·5 g and a higher dose of ampicillin 2 g plus sulbactam 1 g after a one-week period between doses. A reverse-phase highpressure liquid chromatography method was used for the quantitation of ampicillin and sulbactam in serum and urine. The pharmacokinetic parameters for both ampicillin and sulbactam were calculated by computer-based two-compartment nonlinear model. After a 30-min infusion, serum concentrations of both drugs declined in a biexponential manner for both doses. Elderly subjects demonstrated significantly lower total clearances (Clt) than young adult subjects of ampicillin 1 g (22·)± 104·2 vs 36·0±95·8 ml/min/1·73 m2), ampicillin 2g (72·6±36·6 vs 306·8 ± 109·77 ml/min/1·73 m2), sulbactam 0·5 g (122·3 ±47·8 vs 263·9 ±93·7 ml/min/ 1·73 m2), and sulbactam lg (171·2±85·8 vs 391·7±70·8ml/min/1·73m2), respectively. Significance was defined as P < 0·05. Renal clearance was also significantly reduced in the elderly subjects. Area under the curve was found to be significantly increased in the elderly subjects compared to the young subjects for both ampicillin and sulbactam as were the β elimination half-lives. No significant difference in the apparent volume of distribution, when adjusted for body weight, was found for either sulbactam (P > 0·95) or ampicillin (P > 0·95) between the two groups. Linear regression analysis revealed that age was significantly correlated with the Clt, of ampicillin 1 g (r = 0·85, P < 0·001), ampicillin 2 g (r = 0·90, P < 0·001), sulbactam 0·5 g (r = 0·80, P < 0·001), and sulbactam 1 g (r = 0·93, P < 0·001). A multivariate analysis showed a slight improvement in correlation when creatinine clearance was added to age and compared with Clt,. Urinary recovery of both ampicillin and sulbactam was approximately 60% after 14 h.