Influence of the CYP2D6 polymorphism and hemodialysis on codeine disposition in patients with end-stage renal disease.

European Journal of Clinical Pharmacology
Hadi MolanaeiLeif Bertilsson

Abstract

We studied the influence of three factors on drug disposition: genetic polymorphism, impaired renal excretion of drug metabolites, and the possible elimination by hemodialysis (HD), using codeine as a model drug. Based on the genotyping of three CYP2D6 polymorphisms in 228 HD patients, nine extensive metabolizers (EMs) and two poor metabolizers (PMs) were given a single oral dose of 50 mg codeine phosphate. Plasma concentrations of its metabolites codeine-6-glucuronide (C6G), morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) were determined after 2, 4, 6, 8 and 24 h (beginning of the HD session) and again after 4 h of HD (28 h). Codeine metabolites in plasma were quantitated by liquid chromatography-mass spectrometry (LC-MS). The concentrations of C6G in plasma were high and similar in EMs and PMs. Two hours after the codeine intake, the mean concentration of M3G was 210 nM in EMs vs. 3.5 nM in PMs. The M6G metabolite concentrations could be quantitated in EMs but were below the limit of quantification in PMs (<1 nM). All three codeine metabolites/glucuronides remained unchanged or even increased until the start of HD, and thereafter, the concentrations decreased dramatically during the HD procedure. Formation of t...Continue Reading

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Citations

Dec 14, 2011·European Journal of Clinical Pharmacology·Hadi MolanaeiLeif Bertilsson
Oct 9, 2012·Peptides·Richard J Bodnar
Oct 15, 2013·The Laryngoscope·Cynthia A ProwsSenthilkumar Sadhasivam
Jul 27, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Ying GuoCurtis D Klaassen
Mar 20, 2015·Journal of Anaesthesiology, Clinical Pharmacology·Qutaiba A Tawfic, Geoff Bellingham
Oct 9, 2021·Nature Reviews. Nephrology·Daniel G TobinUNKNOWN HOPE Consortium

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