Plasma and cerebrospinal fluid concentrations of morphine and morphine glucuronides after oral morphine. The influence of renal failure.

Abstract

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.

• Authors: G D'Honneur, A Gilton, P Sandouk, J M Scherrmann, P Duvaldestin
• Journal: Anesthesiology (Anesthesiology) Vol. 81 Issue 1 Pg. 87-93 (Jul 1994) ISSN: 0003-3022 [Print] United States
• PMID: 8042814 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Morphine Derivatives
• morphine-6-glucuronide
• Morphine
• morphine-3-glucuronide

Topics

• Administration, Oral
• Aged
• Aged, 80 and over
• Blood-Brain Barrier
• Body Weight (physiology)
• Humans
• Kidney (physiology)
• Middle Aged
• Morphine (administration & dosage, blood, cerebrospinal fluid)
• Morphine Derivatives (blood, cerebrospinal fluid)
• Renal Insufficiency (blood, cerebrospinal fluid, physiopathology)