Pharmacokinetics and metabolism of codeine in humans

✍ Scribed by Dr Tom B. Vree; Corrien P. W. G. M. Verwey-Van Wissen

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 716 KB
• Volume: 13
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510130607

✦ Synopsis

Codeine (30 mg phosphate) was metabolized by eight human volunteers to the following six metabolites: codeine-6-glucuronide 81 .O+ 9.3 per cent, norcodeine 2.16? 1.44 per cent, morphine 0-562 0-39 per cent, morphine-3-glucuronide 2-10? 1-24 per cent, morphine-6-glucuronide 0-80k 0.63 per cent, and normorphine 2.44f 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 a47 f 0.32 h, that of codeine-6-glucuronide 2.75 f 0.79 h, and that of morphine-3-glucuronide 1 a71 ? 0-51 h. The systemic clearance of codeine was 2280? 840 ml min-I, the renal clearance of codeine was 93.8 k 29-8 ml rnin-', and that of codeine-6-glucuronide was 122f 39.2 ml min-'. 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 34.0f3.6 per cent, respectively. The in vitro protein binding of norcodeine was 23-5k2.9 per cent; of morphine, 46.5? 2.4 per cent; of normorphine, 23.5 k3.5 per cent; of morphine-3-glucuronide, 27 -0k 0.8 per cent; and of morphine-6-glucuronide, 36.7k3.8 per cent.