VANCOMYCIN PHARMACOKINETICS, RENAL HANDLING, AND NONRENAL CLEARANCES IN NORMAL HUMAN-SUBJECTS
VANCOMYCIN PHARMACOKINETICS, RENAL HANDLING, AND NONRENAL CLEARANCES IN NORMAL HUMAN-SUBJECTS
复制标题
DOI：
10.1038/clpt.1988.74
复制
发表时间：
1988-05-01
影响因子：
6.7
通讯作者：
BENNETT, WM
中科院分区：
文献类型：
--
作者：
GOLPER, TA;NOONAN, HM;BENNETT, WM
万古霉素的肾脏处理尚不清楚。先前报道的研究尚未达到万古霉素浓度恒定的稳态条件。我们在 9 名健康受试者中，在稳态血清万古霉素浓度为 7 和 14 mg/L 时，同时测量了万古霉素的全身清除率以及万古霉素、肌酐、菊粉和对氨基马尿酸盐的肾脏清除率。对于所有稳态观察结果，万古霉素的肾清除率为 89.+-。 11 ml/min（平均值.+-. SE），菊粉清除率105 .+-. 9ml/min，肌酐清除率117.+-。 9ml/min，副主马尿酸的清除率496.+-。 41 毫升/分钟。万古霉素的全身清除率为131.+/-。 7 毫升/分钟。在两种稳态万古霉素浓度下，肌酐、菊粉和对氨基马尿酸的清除率以及万古霉素的肾清除率没有统计学差异。万古霉素的肾脏清除率与菊粉的清除率之比为0.89±。 0.06 和肌酐清除率 0.79 .+-。 0.05。两个比率均独立于万古霉素浓度、尿流速和滤过分数。由于非肾清除率增加，万古霉素血清浓度为 14 mg/L 时的万古霉素全身清除率比 7 mg/L 时高 10% (p < 0.05)。因此，在健康受试者中，30%的全身万古霉素清除是通过非肾脏机制进行的，并且这种非肾脏清除是浓度依赖性的。假设蛋白结合率在 10% 至 20% 之间，则万古霉素的肾脏排泄主要通过肾小球滤过。这些技术不能排除少量的管状万古霉素转运。
The renal handling of vancomycin is unknown. Previously reported studies have not achieved steady-state conditions with constant vancomycin concentrations. We measured systemic vancomyin clearance simultaneously with the renal clearances of vancomycin, creatinine, inulin, and para-aminohippurate in nine healthy subjects at steady-state serum vancomycin concentrations of 7 and 14 mg/L. For all steadystate observations the renal clearance of vancomycin was 89 .+-. 11 ml/min (mean .+-. SE), the clearance of inulin 105 .+-. 9 ml/min, the clearance of creatinine 117 .+-. 9 ml/min, and the clearance of paramainohippuric acid 496 .+-. 41 ml/min. The systemic clearance of vancomycin was 131 .+-. 7 ml/min. The clearances of creatinine, inulin, and para-aminohippuric acid and the renal clearance of vancomycin were not statistically different at both steady-state vancomycin concentrations. The ratio of the renal clearance of vancomycin to the clearance of inulin was 0.89 .+-. 0.06 and to creatinine clearance 0.79 .+-. 0.05. Both ratios were independent of vancomycin concentration, urine flow rate, and filtration fraction. The systemic clearance of vancomycin was 10% greater at serum vancomycin concentrations of 14 mg/L than at 7 mg/L (p < 0.05) because of an increase in the nonrenal clearance. Therefore in healthy subjects, 30% of the systmic vancomycin clearance is by nonrenal mechanisms and this nonrenal clearance is concentration dependent. Assuming protein binding to be between 10% and 20%, renal vancomycin excretion is predominantly by glomerular filtration. Small amounts of tubular vancomycin transport cannot be excluded by these techniques.