Smith D E, Gambertoglio J G, Vincenti F, Benet L Z
Clin Pharmacol Ther. 1981 Jul;30(1):105-13. doi: 10.1038/clpt.1981.134.
We examined differences between responder (R) (40 to 80 mg/day) and nonresponder (NR) (greater than or equal to 120 mg/day) patients after kidney transplant with respect to furosemide kinetics and dynamics. Nonresponders had reduced plasma clearance (NR 64 +/- 21.4 and R 105 +/- 23 ml/min, two-sample t test; p less than 0.05), renal clearance (NR 18.4 +/- 8.1 and R 47.1 +/- 11.0 ml/min; p less than 0.005), and renal clearance to creatinine clearance ratio (NR 0.43 +/- 0.15 and R 0.80 +/- 0.07; p less than 0.005). Half-life rose in the nonresponders (NR 130 +/- 13 and R 87.6 +/- 16.3 min; p less than 0.005). There was no difference between groups with respect to nonrenal clearance, extent of availability, volume of distribution steady state, and the fraction of the dose excreted unchanged in the urine after intravenous administration. These results suggest that nonresponders have less ability to secrete furosemide into tubular fluid as well as less ability to respond to drug.
我们研究了肾移植后速尿药代动力学和药效学方面反应者(R)(40至80毫克/天)和无反应者(NR)(大于或等于120毫克/天)患者之间的差异。无反应者的血浆清除率降低(NR 64±21.4,R 105±23毫升/分钟,两样本t检验;p<0.05),肾清除率降低(NR 18.4±8.1,R 47.1±11.0毫升/分钟;p<0.005),以及肾清除率与肌酐清除率之比降低(NR 0.43±0.15,R 0.80±0.07;p<0.005)。无反应者的半衰期升高(NR 130±13,R 87.6±16.3分钟;p<0.005)。在非肾清除率、药物可利用程度、稳态分布容积以及静脉给药后尿液中以原形排泄的剂量分数方面,两组之间没有差异。这些结果表明,无反应者将速尿分泌到肾小管液中的能力较低,对药物的反应能力也较低。