The pharmacokinetics of codeine and its metabolites in Blacks with sickle cell disease.
PURPOSE: We conducted a prospective, open-label study in 54 adult subjects with sickle cell disease to determine the relationship between morphine concentrations, cytochrome P450 (CYP) 2D6 genotype, and clinical outcomes. METHODS: A blood sample was obtained for genotyping and serial blood samples w...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 65; no. 7; pp. 651 - 659 |
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| Autores principales: | , , , , , , , , |
| Formato: | clinical trial equations & formulas research tables/charts Journal Article |
| Publicado: |
Springer Nature
Jul2009
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105355258&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105355258 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Jul2009 vid: 65 iid: 7 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 105355258 2010313445 10.1007/s00228-009-0646-3 NLM19357842 105355258 ppf: 651 ppct: 8 formats: fmt: @attributes: type: P tig: atl: The pharmacokinetics of codeine and its metabolites in Blacks with sickle cell disease. aug: au: Shord SS Cavallari LH Gao W Jeong H Deyo K Patel SR Camp JR Labott SM Molokie RE affil: Department of Pharmacy Practice, University of Illinois, College of Pharmacy (MC 886), 833 S Wood Street, Room 164, Chicago, IL 60612, USA. sshord@uic.edu sug: subj: Anemia, Sickle Cell Therapy Codeine Pharmacokinetics Anemia, Sickle Cell Familial and Genetic Black Persons Clinical Trials Consent Data Analysis Software Enzymes Pharmacokinetics Fisher's Exact Test Funding Source Morphine Physiology Pharmacy and Pharmacology Wilcoxon Rank Sum Test Human ab: PURPOSE: We conducted a prospective, open-label study in 54 adult subjects with sickle cell disease to determine the relationship between morphine concentrations, cytochrome P450 (CYP) 2D6 genotype, and clinical outcomes. METHODS: A blood sample was obtained for genotyping and serial blood samples were drawn to measure codeine and its metabolites in the plasma before and after oral codeine sulfate 30 mg. Codeine and its metabolites were measured by liquid chromatography-tandem mass spectrometry (LC-MS). CYP2D6 genetic testing included four single nucleotide polymorphisms (SNP) indicative of three variant alleles: *17 (1023T); *29 (1659A, 3183A); and *41 (2988A) alleles. RESULTS: Thirty subjects (group I) had a mean (standard deviation) maximal morphine concentration of 2.0 (1.0) ng/ml. Morphine was not measurable in the remaining 24 subjects (group II). Nine (30%) subjects in group I and 11 (46%) subjects in group II carried a variant *17, *29, or *41 allele (p = 0.23); one (3%) subject in group I and 5 (21%) subjects in group II were homozygous for *17 or *29 allele (p = 0.07). Emergency room visits (group I 1.5 +/- 1.8 vs. group II 2.1 +/- 4.3, p = NS) did not differ based on metabolic status, but more hospital admissions (0.9 +/- 1.4 vs. 2.2 +/- 4.1, p = 0.05) were documented in patients with no measurable morphine concentrations. CONCLUSIONS: We conclude that Blacks with sickle cell disease without measurable plasma morphine levels after a single dose of codeine were not more likely to be a carrier of a single variant allele commonly associated with reduced CYP2D6 metabolic capacity; however, homozygosity for a variant CYP2D6 allele may result in reduced metabolic capacity. Furthermore, it appears that subjects without measurable morphine concentrations were more likely to be admitted to the hospital for an acute pain crisis. pubtype: Academic Journal doctype: clinical trial equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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