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In this review, a number of theoretical bases and regulatory framework are presented for drug–drug interactions (DDIs), with emphasis on those related to absorption and distribution. Also presented is an industry perspective on how to approach these issues in support of drug development. Overall, holistic integration and understanding of the pharmaceutical (e.g., pH-dependent solubility) and pharmacological (e.g., gastrointestinal physiology and therapeutic margin) profiles, as well as pharmacokinetics and underlying absorption and disposition determinants (e.g., clearance, volume of distribution, permeability and protein binding) of drug candidates in various clinical setting should be considered as this can be valuable in ensuring the safe and effective use of new drugs.

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