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

Abstract

The pharmacokinetics of intravenous ampicillin and sulbactam, a beta-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 high-pressure 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 (220.0 +/- 104.2 vs 360.0 +/- 95.8 ml/min/1.73 m2), ampicillin 2 g (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 1 g (171.2 +/- 85.8 vs 391.7 +/- 70.8 ml/min/1.73 m2), respectively. Significance was defined as P less than 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 beta elimination half-lives. No significant difference in the apparent volume of distribution, when adjusted for body weight, was found for either sulbactam (P greater than 0.95) or ampicillin (P greater than 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 less than 0.001), ampicillin 2 g (r = 0.90, P less than 0.001), sulbactam 0.5 g (r = 0.80, P less than 0.001), and sulbactam 1 g (r = 0.93, P less than 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.

Pharmacokinetics of ampicillin-sulbactam in healthy elderly and young volunteers

“…In our study, the mean levels in serum of both ampicillin This is similar to the findings of another reported study (14). and sulbactam (P = 0.0001) and the Cmax were also greatest for group 3 (P = NS).…”

“…and sulbactam (P = 0.0001) and the Cmax were also greatest for group 3 (P = NS). Our data is comparable to that previously reported (14); however, in that study, the t1/2 for the subjects was greater. This observation may be explained by the greater age of their group and age-associated decline in renal function.…”

“…The calculated CLCR was significantly lower for group 3. This is not unexpected, since renal function is known to decrease with age (11,14).…”

“…Prior investigations have suggested that middle-aged adults should be studied (14) to determine the impact of age and CLCR on pharmacokinetic parameters. While we noted differences in CLCR between the elderly group and both younger adult groups, there were no differences in CLCR between middle-aged and younger adults (P = NS).…”

“…Sulbactam is a beta-lactam agent that acts as an irreversible inhibitor of beta-lactamase activity by combining with the enzyme and rendering it inactive. The pharmacokinetics of ampicillin-sulbactam in the elderly have not been extensively studied (5,14). In this study, we examined the pharmacokinetic parameters of ampicillin-sulbactam in three healthy groups: elderly, middle-aged, and younger subjects.…”