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The pharmacokinetics of codeine and its metabolites in Blacks with sickle cell disease

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Abstract

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 30mg. 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.

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Acknowledgements

We would like to extend our gratitude to Dr. Andrea Gaedigk who provided her expertise during the completion of this study.

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Authors and Affiliations

  1. Department of Pharmacy Practice, University of Illinois, College of Pharmacy (MC 886), 833 S Wood Street, Room 164, Chicago, IL, 60612, USA

    Stacy S. Shord, Larisa H. Cavallari, Hyun-Young Jeong, Kelly Deyo, Shitalben R. Patel & Joseph R. Camp

  2. Department of Psychiatry, University of Illinois, College of Medicine (MC 913), 912 S Wood Street, Chicago, IL, USA

    Susan M. Labott

  3. Department of Medicine, Section of Hematology/Oncology, University of Illinois, College of Medicine (MC 713), 840 S Wood Street, Chicago, IL, USA

    Robert E. Molokie

  4. University of Illinois School of Public Health, Chicago, IL, USA

    Weihua Gao

  5. University of Illinois Sickle Cell Center, Chicago, IL, USA

    Susan M. Labott & Robert E. Molokie

Authors
  1. Stacy S. Shord
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  2. Larisa H. Cavallari
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  3. Weihua Gao
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  4. Hyun-Young Jeong
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  5. Kelly Deyo
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  6. Shitalben R. Patel
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  7. Joseph R. Camp
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  8. Susan M. Labott
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  9. Robert E. Molokie
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Corresponding author

Correspondence to Stacy S. Shord.

Additional information

This study was supported in part by the Illinois Department of Public Health awarded to the Sickle Cell Center, Janssen Medical Affairs, LLC (FEN-EMR4007) and a Clinical Translational Science Award from the Center for Clinical Translational Science at the University of Illinois awarded to Dr. Stacy S. Shord and the General Clinical Research Center at the University of Illinois Medical Center at Chicago (NIH grant M01-RR-13987).

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Shord, S.S., Cavallari, L.H., Gao, W. et al. The pharmacokinetics of codeine and its metabolites in Blacks with sickle cell disease. Eur J Clin Pharmacol 65, 651–658 (2009). https://doi.org/10.1007/s00228-009-0646-3

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  • DOI: https://doi.org/10.1007/s00228-009-0646-3

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