Dowell J A, Korth-Bradley J, Milisci M, Tantillo K, Amorusi P, Tse S
Clinical Pharmacokinetics, Wyeth-Ayerst Research, Radnor, Pennsylvania, USA.
J Clin Pharmacol. 2001 Sep;41(9):979-86. doi: 10.1177/00912700122010960.
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.
进行了一项研究，以进一步调查在肾功能损害患者中，妥布霉素与哌拉西林/他唑巴坦合用时明显的不稳定性。研究了26名年龄在23至74岁之间的健康志愿者。8名受试者有中度肾功能损害，10名有轻度肾功能损害，8名肾功能正常。每位受试者接受单剂量的哌拉西林/他唑巴坦和妥布霉素，以及联合剂量，采用随机、三交叉设计。肾功能正常的受试者还接受了哌拉西林和妥布霉素的联合剂量。采集后，采取了相当谨慎的措施防止血浆和尿液样本的体外失活。未观察到药代动力学参数的系统性变化。得出的结论是，单独使用哌拉西林或与他唑巴坦合用，在肾功能损害患者中均不会改变妥布霉素的药代动力学。其他人报道的在哌拉西林或哌拉西林/他唑巴坦存在下妥布霉素明显的体内失活可能是体外失活的假象。
