A de la Pena1, H Derendorf. 1. Department of Pharmaceutics, University of Florida, Gainesville 32610, USA.
Abstract
OBJECTIVES: In recent years, the use of combinations of beta-lactam-antibiotics with beta-lactamase inhibitors has been proven to be a useful and effective strategy to improve upon the therapeutic value of beta-lactam antibiotics. The objective of this article is to evaluate the pharmacokinetic properties of three commercially available beta-lactamase inhibitors. MATERIALS AND METHODS: Based on published articles in the literature, the pharmacokinetic properties of the beta-lactamase inhibitors clavulanic acid, sulbactam and tazobactam are reviewed and compared. RESULTS: There are some considerable differences between these three compounds: Only clavulanic acid is orally bioavailable. Tazobactam and sulbactam are eliminated renally to a larger extent than clavulanic acid. Tazobactam's total body clearance is almost twice that of sulbactam, and the two drugs differ significantly in their degree of protein-binding. Furthermore, sulbactam has a larger volume of distribution than tazobactam. CONCLUSIONS: When choosing combinations of a beta-lactam antibiotic with a beta-lactamase inhibitor, it is important to make sure that the pharmacokinetic properties of drug and inhibitor are similar and remain similar under changing pathophysiological conditions. Hence, beta-lactam inhibitors should not be freely interchanged, but for each beta-lactam antibiotic the best partner needs to be identified. If this is done properly, fixed combinations of beta-lactam-antibiotic and beta-lactamase inhibitor are appropriate and convenient. This situation may represent one of the few cases in pharmacotherapy, where fixed combinations of two drugs are beneficial.
OBJECTIVES: In recent years, the use of combinations of beta-lactam-antibiotics with beta-lactamase inhibitors has been proven to be a useful and effective strategy to improve upon the therapeutic value of beta-lactam antibiotics. The objective of this article is to evaluate the pharmacokinetic properties of three commercially available beta-lactamase inhibitors. MATERIALS AND METHODS: Based on published articles in the literature, the pharmacokinetic properties of the beta-lactamase inhibitors clavulanic acid, sulbactam and tazobactam are reviewed and compared. RESULTS: There are some considerable differences between these three compounds: Only clavulanic acid is orally bioavailable. Tazobactam and sulbactam are eliminated renally to a larger extent than clavulanic acid. Tazobactam's total body clearance is almost twice that of sulbactam, and the two drugs differ significantly in their degree of protein-binding. Furthermore, sulbactam has a larger volume of distribution than tazobactam. CONCLUSIONS: When choosing combinations of a beta-lactam antibiotic with a beta-lactamase inhibitor, it is important to make sure that the pharmacokinetic properties of drug and inhibitor are similar and remain similar under changing pathophysiological conditions. Hence, beta-lactam inhibitors should not be freely interchanged, but for each beta-lactam antibiotic the best partner needs to be identified. If this is done properly, fixed combinations of beta-lactam-antibiotic and beta-lactamase inhibitor are appropriate and convenient. This situation may represent one of the few cases in pharmacotherapy, where fixed combinations of two drugs are beneficial.