1 / 10

CYP2B6/CYP2C8 and Drug Interactions: Introduction

Advisory Committee for Pharmaceutical Sciences - Clinical Pharmacology Subcommittee Meeting November 18, 2003, Rockville, MD. CYP2B6/CYP2C8 and Drug Interactions: Introduction . Shiew-Mei Huang, Ph.D. Deputy Director for Science Office of Clinical Pharmacology & Biopharmaceutics

mireya
Download Presentation

CYP2B6/CYP2C8 and Drug Interactions: Introduction

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Advisory Committee for Pharmaceutical Sciences - Clinical Pharmacology Subcommittee Meeting November 18, 2003, Rockville, MD CYP2B6/CYP2C8 andDrug Interactions: Introduction Shiew-Mei Huang, Ph.D. Deputy Director for Science Office of Clinical Pharmacology & Biopharmaceutics CDER, FDA

  2. Drug Interaction Guidance (1999) Revision- • classification of CYP3A inhibitors • P-gp based interactions • in vitro evaluation • labeling implication • Guidance for industry: In vivo metabolism/drug interactions: Study design, data analysis and recommendation for dosing and labeling (Issued 11/24/1999, Posted 11/24/1999); http://www.fda.gov/cder/guidance/index.htm; http://www.fda.gov/cder/guidance/2635fnl.pdf • Tucker, Houston and Huang, Clin Pharm Ther August 2001; 70(2):103 • Bjornsson, Callaghan, Einolf, et al, J Clin Pharmacol, May 2003; 43(5):443 • Yuan, Madani, Wei, Reynolds, Huang, Drug Metab Disp, December 2002; 30(12) 1311 • Labeling guideline. Federal Register 65[247], 81082-81131. December 22, 2000.

  3. In vitro CYP evaluation Current Practices CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A - reaction phenotyping (in addition:2A6, 2B6, 2C8, 2E1) - enzyme modulating effect • In vivo (clinical) evaluation - Prioritized based on in vitro CYP results • other drugs’ effect • effect on other drugs - P-gp based interactions • Other pathways?

  4. Cases of rhabdomyolysis involving gemfibrozil and statins Why CYP2C8? • Pharmacodynamic/pharmacokinetic interaction? • Gemfibrozil does not interact via CYP3A • Other enzymes/transport pathway? - CYP2C8/2C9, UGT, OATP?

  5. Effect of Gemfibrozil Statins AUC ratios c.f. Trimethorprim cerivastatin repaglinide fluvastatin rosuvastatin lovastatin acid rosiglitazone simvastatin acid

  6. Drug A • What CYP2C8 inhibitors available to evaluate clinical significance of this type of interactions? • Metabolized by CYP2C8 in vitro Drug B • Inhibits CYP2C8 in vitro • What CYP2C8 probe substrates to evaluate clinical significance of this type of interactions?

  7. Why CYP2B6? • Recent data on inducers • Recent studies on efavirenz, bupropion Drug C • Metabolized by CYP2B6 in vitro • What CYP2B6 inhibitors available to evaluate clinical significance of this type of interactions?

  8. CYP2B6 and Drug Interactions David A Flockhart, MD, PhD Indiana University CYP2C8 and Drug Interactions Pertti J Neuvonen, MD University of Helsinki

  9. Issues to discuss - • What is the clinical significance of CYP2B6- and CYP2C8- based interactions? • Are there tools available for clinical evaluation of CYP2B6- and CYP2C8 based interactions? • Other areas to focus on?

  10. Drug Interactions working group Sophia Abraham Sayed Al-Habet Sang Chung Phil Colangelo Shiew-Mei Huang Ron Kavanagh Srikanth Nallani Lawrence Lesko Wei Qiu Atik Rahman Kellie Reynolds Xiaoxiong Wei Lei K Zhang Jenny H Zheng Jerry Collins Soloman SobelJohn Strong Martin Green David Frucht Kathy Hollinger

More Related