PLASMA AND CEREBROSPINAL-FLUID CONCENTRATIONS OF MORPHINE AND MORPHINE GLUCURONIDES AFTER ORAL MORPHINE - THE INFLUENCE OF RENAL-FAILURE

被引:64
作者
DHONNEUR, G
GILTON, A
SANDOUK, P
SCHERRMANN, JM
DUVALDESTIN, P
机构
[1] UNIV PARIS,HOP HENRI MONDOR,DEPT ANESTHESIA,SERV ANESTHESIE REANIMAT,F-94010 CRETEIL,FRANCE
[2] INSERM,U26,PARIS,FRANCE
关键词
ANALGESICS; OPIOID; MORPHINE; KIDNEY; RENAL FAILURE; PHARMACOKINETICS; PHARMACOLOGY;
D O I
10.1097/00000542-199407000-00013
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Background: In patients with renal failure, morphine may cause prolonged narcosis and respiratory depression. Accumulation of the pharmacologically active metabolite morphine-6-glucuronide (M-6G) may explain this effect of morphine in patients with renal failure. After a single oral dose, morphine and its conjugates were measured in the plasma and the cerebrospinal fluid (CSF) in patients with renal failure. Methods: Eight patients with normal renal function and six patients with renal failure requiring dialysis were studied after operation under spinal anesthesia. Plasma and CSF concentrations of morphine, morphine-3-glucuronide (M-3G), and M-6G were measured by high-pressure liquid chromatography every 4 h for 24 h after an oral dose of 30 mg morphine. Results: The area under morphine plasma concentration-time curve from 0 to 24 h increased from 38 +/- 4 ng.ml(-1) X h in patients with normal renal function to 110 ng.ml(-1) X h in those with renal failure (P < 0.01). In patients with renal failure, plasma concentrations of M-3G and M-6G were higher at 4 h and remained at an increased level until the end of the study. The peak CSF concentration of morphine at 8 h was similar in those with renal failure or normal renal function, 1.8 +/- 0.4 and 2.0 +/- 0.6 ng ml(-1) respectively. M-3G and M-6G in CSF reached a maximum at 12 h in patients with normal renal function, whereas in those with renal failure the concentrations gradually increased so that the highest concentrations were observed at 24 h. At 24 h, CSF M-6G concentration was 15 times greater in patients with renal failure than in those with normal renal function. Conclusions: We conclude that M-3G and M-6G readily cross the blood-brain barrier in patients with normal renal function or with renal failure. In patients with renal failure, the retention of plasma M-6G induces a progressive accumulation of this active metabolite in CSF; this accumulation may explain the increased susceptibility to morphine in patients with renal failure.
引用
收藏
页码:87 / 93
页数:7
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