title: Pharmacokinetics and metabolism of codeine in humans.
abstract: Codeine (30 mg phosphate) was metabolized by eight human volunteers to the following six metabolites: codeine-6-glucuronide 81.0 +/- 9.3 per cent, norcodeine 2.16 +/- 1.44 per cent, morphine 0.56 +/- 0.39 per cent, morphine-3-glucuronide 2.10 +/- 1.24 per cent, morphine-6-glucuronide 0.80 +/- 0.63 per cent, and normorphine 2.44 +/- 2.42 per cent. Two out of eight volunteers were unable to O-dealkylate codeine into morphine and lack therefore the cytochrome P450 IID6 isoenzyme. The half-life of codeine was 1.47 +/- 0.32 h, that of codeine-6-glucuronide 2.75 +/- 0.79 h, and that of morphine-3-glucuronide 1.71 +/- 0.51 h. The systemic clearance of codeine was 2280 +/- 840 ml min-1, the renal clearance of codeine was 93.8 +/- 29.8 ml min-1, and that of codeine-6-glucuronide was 122 +/- 39.2 ml min-1. The plasma AUC of codeine-6-glucuronide is approximately 10 times higher than that of codeine. Protein binding of codeine and codeine-6-glucuronide in vivo was 56.1 +/- 2.5 per cent and 34.0 +/- 3.6 per cent, respectively. The in vitro protein binding of norcodeine was 23.5 +/- 2.9 per cent; of morphine, 46.5 +/- 2.4 per cent; of normorphine, 23.5 +/- 3.5 per cent; of morphine-3-glucuronide, 27.0 +/- 0.8 per cent; and of morphine-6-glucuronide, 36.7 +/- 3.8 per cent.
authors.affiliation: Department of Clinical Pharmacy, Academic Hospital Nijmegen Sint Radboud, The Netherlands.
authors.forename: T B
authors.initials: TB
authors.lastname: Vree
authors.forename: C P
authors.initials: CP
authors.lastname: Verwey-van Wissen
mesh_terms: D000328:Adult; D003061:Codeine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000378:metabolism; D009022:Morphine Derivatives / Q000378:metabolism; D011485:Protein Binding
chemical_list: D009022:Morphine Derivatives; C010414:norcodeine; C035349:morphine-6-glucuronide; D009020:Morphine; C061773:codeine-6-glucuronide; C018108:morphine-3-glucuronide; D003061:Codeine