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.