Review of Pharmacokinetic Data of Different Drug Classes in Goto-Kakizaki Rats, a Non-obese Model for Type 2 Diabetes Mellitus: Case Studies and Perspectives

Goto-Kakizaki (GK) rats represent a unique nonobese and lean model with manifestation of type 2 diabetes (T2DM) broadly mimicking the human T2DM development. Therefore, in addition to the use of GK rats to test the efficacy of drugs, it may represent a great tool to study the influence of altered physiological process and/ or organ specific pathophysiological changes (i.e., liver, kidney, etc.) on the disposition of drugs. The objectives of the review were: (a) to compile the published pharmacokinetic data of several drugs, such as cephalexin, cyclosporine, exendin-4, gliclazide, grepafloxacin, rosuvastatin, salsalate, salicylic acid, and theophylline, in GK rats relative to normal rats; and (b) critically evaluate the possible role of physiologically altered processes on the pharmacokinetics of reviewed drugs. The drugs chosen for this review provided a spread of various physiological processes and represented reasonable pool of published data set to fulfil the objectives of the review. The use of GK rats for gathering pharmacokinetic data may aid in making decisions on candidate selection and/ or anticipating clinical pharmacology-related issues to the aid drug development in the diabetes area. However, given the interplay and complexities of multiple pathways governing drug disposition, caution needs to be exercised in data interpretation.