Altered tobramycin pharmacokinetics during chemoprophylaxis in bladder surgery

Abstract

The effect of bladder surgery on the pharmacokinetics of tobramycin in hospitalized patients was studied. Fourteen patients with vesical neoplasia undergoing urinary tract surgery were given tobramycin in a dose of 2 mg/kg of body weight. Each patient received the dose at the induction of anesthesia, about 1 h before surgical incision. For seven patients, the drug was also administered 3 weeks later when nutritional conditions were normal. The pharmacokinetic parameters were determined by a two-compartment open model. Except for renal clearance, no significant difference appeared between pharmacokinetic parameters determined from serum data during peri- and postoperative periods. During this work, tobramycin excretion in urine was studied. Twenty-four hours after drug administration, the mean urine tobramycin levels were 25.5 +/- 9.06 and 41.6 +/- 21.5 micrograms/ml after peri- and postoperative administration, respectively; these values were higher than the MICs for most urinary tract pathogens. Seventy-two hours after perioperative administration, the mean value was still elevated (3.54 micrograms/ml), but 72 h after postoperative administration, the urinary tobramycin concentration was not detectable. The percentages of tobramycin recovered unchanged in urine were 54 and 79% after peri- and postoperative administration, respectively. When tobramycin was administered during surgery, a long terminal log-linear phase, with a mean half-life of 25.6 h, was detected. The ratio of renal clearance to total body clearance was 0.52 and 0.79 after peri- and postoperative administration, respectively.