Systematic and quantitative assessment of the effect of chronic kidney disease on CYP2D6 and CYP3A4/5

K. Yoshida, B. Sun, L. Zhang, P. Zhao, D. R. Abernethy, T. D. Nolin, A. Rostami-Hodjegan, I. Zineh, S. M. Huang

Research output: Contribution to journalArticle

Abstract

Recent reviews suggest that chronic kidney disease (CKD) can affect the pharmacokinetics of nonrenally eliminated drugs, but the impact of CKD on individual elimination pathways has not been systematically evaluated. In this study we developed a comprehensive dataset of the effect of CKD on the pharmacokinetics of CYP2D6- and CYP3A4/5-metabolized drugs. Drugs for evaluation were selected based on clinical drug-drug interaction (CYP3A4/5 and CYP2D6) and pharmacogenetic (CYP2D6) studies. Information from dedicated CKD studies was available for 13 and 18 of the CYP2D6 and CYP3A4/5 model drugs, respectively. Analysis of these data suggested that CYP2D6-mediated clearance is generally decreased in parallel with the severity of CKD. There was no apparent relationship between the severity of CKD and CYP3A4/5-mediated clearance. The observed elimination-route dependency in CKD effects between CYP2D6 and CYP3A4/5 may inform the need to conduct clinical CKD studies with nonrenally eliminated drugs for optimal use of drugs in patients with CKD.

Original languageEnglish (US)
Pages (from-to)75-87
Number of pages13
JournalClinical pharmacology and therapeutics
Volume100
Issue number1
DOIs
StatePublished - Jul 1 2016

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Yoshida, K., Sun, B., Zhang, L., Zhao, P., Abernethy, D. R., Nolin, T. D., Rostami-Hodjegan, A., Zineh, I., & Huang, S. M. (2016). Systematic and quantitative assessment of the effect of chronic kidney disease on CYP2D6 and CYP3A4/5. Clinical pharmacology and therapeutics, 100(1), 75-87. https://doi.org/10.1002/cpt.337