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 tobramycin 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, 10 had mild renal impairment, and 8 had normal renal function. Each subject received single doses of piperacillin/tazobactam and tobramycin alone as well as combined doses in a randomized, three-way crossover design. The subjects with normal renal function also received combined doses of piperacillin and tobramycin. Considerable care was taken to protect against in vitro inactivation of plasma and urine samples after collection. No systematic changes in pharmacokinetic parameters were observed. It is concluded that piperacillin, either alone or with tazobactam, did not change the pharmacokinetics of tobramycin in subjects with renal impairment. The apparent in vivo inactivation of tobramycin in the presence of piperacillin or piperacillin/tazobactam reported by others may be an artifact of ex vivo inactivation.
Dowell
J A
JA
Clinical Pharmacokinetics, Wyeth-Ayerst Research, Radnor, Pennsylvania, USA.
Korth-Bradley
J
J
Milisci
M
M
Tantillo
K
K
Amorusi
P
P
Tse
S
S
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003404:Creatinine / Q000652:urine; D018592:Cross-Over Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D010406:Penicillins / Q000493:pharmacokinetics*; D010878:Piperacillin / Q000493:pharmacokinetics*; D000078142:Tazobactam; D014031:Tobramycin / Q000493:pharmacokinetics*; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D010406:Penicillins; D065093:beta-Lactamase Inhibitors; D010397:Penicillanic Acid; D003404:Creatinine; D000078142:Tazobactam; D014031:Tobramycin; D010878:Piperacillin