Abstract

PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELLING APPROACH FOR CLINICAL RESEARCH ON TACROLIMUS

Mohd. Akhtar*, Sajad Khaliq Dar, Arshad H. Khuroo and Ramakrishna Vydana

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Abstract

Tacrolimus is an effective immunosuppressant that reduces the risk of organ transplant rejection. Despite being the drug of choice, there are numerous challenges such as the narrow therapeutic index, high pharmacokinetics and pharmacodynamic variability, drug and food interactions etc. associated with its use. Therefore, model-informed drug development becomes essential to support such drugs at different stages of research and clinical application. This review highlights the need for physiologically based pharmacokinetic (PBPK) modelling in the research and development of drugs like Tacrolimus. The applications of PBPK to evaluate drug-drug interactions, facilitate first-in-human dose estimations, drug-food interactions, biopharmaceutical risks, selection of suitable drug candidates based on biopharmaceutical properties, requirement of fasting and fed state for bioequivalence study, clinical study waivers for lower strengths, critical bioavailability attributes, impact of demography, and to support regulatory filings etc. have made this approach a building block of drug research and development.

Keywords: Tacrolimus, Pharmacokinetics, Pharmacodynamics, Drug Interactions, PBPK, Model informed drug development.