Evaluating possible pharmacokinetic interactions between tobramycin, piperacillin, and a combination of piperacillin and tazobactam in patients with various degrees of renal impairment

A study was performed to further investigate the apparent instability of to bramycin when coadministered with piperacillin/tazobactam in subjects with renal impairment, Twenty-six otherwise healthy volunteers between 23 and 74 years of age were studied. Eight subjects had moderate renal impairment, 1 0 had mild renal impairment, and 8 had normal renal function. Each subject received single doses of piperacillin/tazobactam and tobramycin alone as we ll as combined doses in a randomized, three-way crossover design. The subje cts with normal renal function also received combined doses of piperacillin and tobramycin. Considerable care was taken to protect against in vitro in activation of plasma and urine samples after collection. No systematic chan ges in pharmacokinetic parameters were observed. It is concluded that piper acillin, either alone or with tazobactam, did not change the pharmacokineti cs of tobramycin in subjects with renal impairment. The apparent in vivo in activation of tobramycin in the presence of piperacillin or piperacillin/ta zobactam reported by others may be an artifact of ex vivo inactivation. (C) 2001 the American College of Clinical Pharmacology.