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Review
. 2009 Jun;11(2):300-6.
doi: 10.1208/s12248-009-9106-3. Epub 2009 May 6.

Predicting drug-drug interactions: an FDA perspective

Lei Zhang  1 , Yuanchao Derek Zhang, Ping Zhao, Shiew-Mei Huang
Affiliations
Review

Predicting drug-drug interactions: an FDA perspective

Lei Zhang et al. AAPS J. 2009 Jun.

Abstract

Pharmacokinetic drug interactions can lead to serious adverse events, and the evaluation of a new molecular entity's drug-drug interaction potential is an integral part of drug development and regulatory review prior to its market approval. Alteration of enzyme and/or transporter activities involved in the absorption, distribution, metabolism, or excretion of a new molecular entity by other concomitant drugs may lead to a change in exposure leading to altered response (safety or efficacy). Over the years, various in vitro methodologies have been developed to predict drug interaction potential in vivo. In vitro study has become a critical first step in the assessment of drug interactions. Well-executed in vitro studies can be used as a screening tool for the need for further in vivo assessment and can provide the basis for the design of subsequent in vivo drug interaction studies. Besides in vitro experiments, in silico modeling and simulation may also assist in the prediction of drug interactions. The recent FDA draft drug interaction guidance highlighted the in vitro models and criteria that may be used to guide further in vivo drug interaction studies and to construct informative labeling. This report summarizes critical elements in the in vitro evaluation of drug interaction potential during drug development and uses a case study to highlight the impact of in vitro information on drug labeling.

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Figures

Fig. 1
Fig. 1
Distribution of metabolism and transport pathways for NMEs approved between 2003 and 2008 intended for oral administration
See this image and copyright information in PMC

References

    1. Huang SM, Temple R. Is this the drug or dose for you? Impact and consideration of ethnic factors in global drug development, regulatory review, and clinical practice. Clin Pharmacol Ther. 2008;84(3):287–284. doi: 10.1038/clpt.2008.144. - DOI - PubMed
    1. Huang SM, Temple R, Throckmorton DC, Lesko LJ. Drug interaction studies: study design, data analysis, and implications for dosing and labeling. Clin Pharmacol Ther. 2007;81(2):298–304. doi: 10.1038/sj.clpt.6100054. - DOI - PubMed
    1. Huang SM, Strong JM, Zhang L, Reynolds KS, Nallani S, Temple R, Abraham S, Al HS, Baweja RK, Burckart GJ, Chung S, Colangelo P, Frucht D, Green MD, Hepp P, Karnaukhova E, Ko HS, Lee JI, Marroum PJ, Norden JM, Qiu W, Rahman A, Sobel S, Stifano T, Thummel K, Wei XX, Yasuda S, Zheng JH, Zhao H, Lesko LJ. New era in drug interaction evaluation: US food and drug administration update on CYP enzymes, transporters, and the guidance process. J Clin Pharmacol. 2008;48(6):662–670. doi: 10.1177/0091270007312153. - DOI - PubMed
    1. Guidance for Industry: Drug metabolism/drug interactions in the drug development process: studies in vitro. http://www.fda.gov/cder/guidance.
    1. In vivo drug metabolism/drug interaction studies—study design, data analysis, and recommendations for dosing and labeling. http://www.fda.gov/cder/guidance.

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