Morphine-6-Glucuronide Disposition in Renal Impairment

Abstract

Twelve patients with chronic renal failure (dialysis-dependent) and six with good renal function after renal transplantation received i.v. morphine-6-glucuronide (M6G) 30 micrograms kg-1 as part of a standardized anaesthetic technique for minor surgery. Continuous peritoneal dialysis was commenced 6 h after M6G administration in six of the dialysis-dependent patients. Serum was sampled for up to 12 h and analysed for morphine and M6G by high pressure liquid chromatography. Morphine was not detected. Mean (SD) derived pharmacokinetic variables for the three groups (transplant, renally impaired non-dialysed and renally impaired dialysed, respectively) were: elimination half-life 2.14 (0.69) h, 27.10 (15.8) h, 17.33 (4.6) h; clearance 96.0 (34.9) ml min-1, 10.57 (5.57) ml min-1, 14.3 (6.2) ml min-1; volume of distribution 0.19 (0.03) litre kg-1, 0.25 (0.06) litre kg-1, 0.27 (0.06) litre kg-1. The elimination half-life was shorter (P < 0.01) and the clearance greater (P < 0.01) for the transplanted group compared with the dialysed and non-dialysed groups. Peritoneal dialysis for the second 6 h after drug administration had little effect on M6G disposition as assessed by comparison with data obtained from the non-dialysed group.

The pharmacokinetics of the interstitial space in humans

“…al. [47] for morphine-6-glucuronide. Because of the low clearance rate in these subjects, measurements can be extended for longer times (720 minutes for morphine-6-glucuronide and 1440 minutes for amoxicillin) then those used in Table 1.…”

A study of ethyl glucuronide in post-mortem blood as a marker of ante-mortem ingestion of alcohol

“…He suffered from kidney disease, which could cause delayed excretion and therefore considerably lengthen the half lives of the conjugated ethanol metabolites. This effect of kidney disease is described for excretion of other glucuronides, for example, those of morphine (171)(172)(173). This individual also suffered from hepatic disease (hepatitis B and C), but this should not, in theory, cause prolonged half lives.…”

The Prevalence and Management of Chronic Pain in End-Stage Renal Disease

“…[42][43][44][45][46] Toxicity is likely caused by the accumulation of the active metabolites morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G). 47 Because of these difficulties, alternative strong opioids are recommended to manage severe pain in patients with ESRD (Table 2). It has been suggested that hydromorphone, methadone, and fentanyl are better tolerated with safer profiles in this patient population.…”