Pharmacokinetics of morphine are not altered in subjects with Gilbert's syndrome

Aims To verify that Gilbert's syndrome, which is caused by decreased glucuronidation capacity of the UDP-glucuronosyl transferase (UGT)1A1, does not account for impaired morphine clearance. Methods Noncompartmental pharmacokinetic parameters for morphine and its glucuronide metabolites were compared between five carriers of Gilbert's syndrome and six noncarriers after a 7.5 mg (19.8 mumol) intravenous injection of morphine sulphate pentahydrate. To estimate the amount of morphine-6-glucuronide (M6G) formed from morphine, 1 mg of deuterized M6G was injected intravenously at the same time. Results No differences were detected between carriers and noncarriers of Gilbert's syndrome in the clearance of morphine (80.1+/-12 l h(-1) vs 87.9+/-22 l h(-1)) and in the percentage of morphine that was metabolized to M6G (10.9+/-1.4 vs 13+/-2). The areas under the plasma concentration vs time curves of morphine, M6G and morphine-3-glucuronide also did not differ between carriers and noncarriers of Gilbert's syndrome. Conclusions Gilbert's syndrome is not a factor to be considered when prescribing morphine.