Pharmacokinetics of morphine are not altered in subjects with Gilbert's syndrome.
OBJECTIVE
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 micro mol) 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.
Skarke
Carsten
C
pharmazentrum frankfurt, Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. skarke@em.uni-frankfurt.de
Schmidt
Helmut
H
Geisslinger
Gerd
G
Darimont
Jutta
J
Lötsch
Jörn
J
D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005878:Gilbert Disease / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009294:Narcotics / Q000493:pharmacokinetics*
D000701:Analgesics, Opioid; D009294:Narcotics; D009020:Morphine