Bressolle F, Joubert P, Gouby A, Costa P, Laracine M, Rebière T
Département de Pharmacocinétique, Faculté de Pharmacie, Université de Montpellier I, France.
Antimicrob Agents Chemother. 1991 Jul;35(7):1454-9. doi: 10.1128/AAC.35.7.1454.
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.
研究了膀胱手术对住院患者妥布霉素药代动力学的影响。14例接受尿路手术的膀胱肿瘤患者接受了2mg/kg体重剂量的妥布霉素。每位患者在麻醉诱导时,即手术切口前约1小时给予该剂量。7例患者在3周后营养状况正常时也给予了该药物。药代动力学参数由二室开放模型确定。除肾脏清除率外,围手术期和术后血清数据测定的药代动力学参数之间无显著差异。在此研究过程中,对妥布霉素的尿排泄情况进行了研究。给药24小时后,围手术期和术后给药后尿妥布霉素平均水平分别为25.5±9.06和41.6±21.5μg/ml;这些值高于大多数尿路病原体的最低抑菌浓度。围手术期给药72小时后,平均值仍升高(3.54μg/ml),但术后给药72小时后,尿妥布霉素浓度无法检测到。围手术期和术后给药后,尿中回收的未变化妥布霉素百分比分别为54%和79%。手术期间给予妥布霉素时,检测到一个长的终末对数线性期,平均半衰期为25.6小时。围手术期和术后给药后,肾脏清除率与全身清除率的比值分别为0.52和0.79。