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Strategies for preclinical pharmacokinetic investigation in streptozotocin-induced diabetes mellitus (DMIS) and alloxan-induced diabetes mellitus (DMIA) rat models: case studies and perspectives

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Abstract

Preclinical rodent models that manifest type 2 diatetes mellitus using either streptozotocin (DMIS) or alloxan (DMIA) have been well established. Both DMIS and DMIA models have served as key experimental tools to evaluate and understand the pharmacokinetic disposition of scores of drugs and therefore some key questions with respect to absorption, metabolism or elimination of drugs can be answered during the development of full-blown diabetes in the animal models. The choice of the right preclinical rodent model and adaptation of the appropriate experimental design could help to generate data to enable go or no-go decision on the clinical candidate. Also, such models may help to understand the risk potential from a drug–drug interaction perspective. The review provides an overview of the strategies and perspectives of institutionalizing DMIS and/or DMIA rat models using relevant case studies.

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  1. Nuggehally R. Srinivas

    Present address: Semler Research Center, Specialty Pharmaceuticals, JP Nagar 6th Phase, Bangalore, 560078, India

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  1. Pharmacokinetics and Biopharmaceutics, Dr Reddy’s Institute of Life Sciences, Gachibowli, Hyderabad, 500046, India

    Nuggehally R. Srinivas

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Srinivas, N.R. Strategies for preclinical pharmacokinetic investigation in streptozotocin-induced diabetes mellitus (DMIS) and alloxan-induced diabetes mellitus (DMIA) rat models: case studies and perspectives. Eur J Drug Metab Pharmacokinet 40, 1–12 (2015). https://doi.org/10.1007/s13318-014-0186-9

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