Use of Physiologically Based Pharmacokinetic Modeling to Evaluate the Impact of Chronic Kidney Disease on CYP3A4‐Mediated Metabolism of Saxagliptin

• Published in: Journal of clinical pharmacology Vol. 62; no. 8; pp. 1018 - 1029
• Main Authors: Butrovich, Morgan A., Tang, Weifeng, Boulton, David W., Nolin, Thomas D., Sharma, Pradeep
• Format: Journal Article
• Language: English
• Published: England 01.08.2022
• Subjects: chronic kidney disease; CYP3A; CYP3A4; cytochrome P450 3A4; nonrenal clearance; physiologically based pharmacokinetic modeling; nonrenal clearance; CYP3A; chronic kidney disease; cytochrome P450 3A4; CYP3A4; physiologically based pharmacokinetic modeling

We characterized the impact of chronic kidney disease (CKD) on the cytochrome P450 (CYP) 3A4–mediated metabolism of saxagliptin to its metabolite, 5‐hydroxysaxagliptin, using a physiologically based pharmacokinetic (PBPK) model. A PBPK model of saxagliptin and its CYP3A4 metabolite, 5‐hydroxysaxagli...