Lecturer University of Manchester Manchester, England, United Kingdom
Presentation Description: Creatinine is widely used as a biomarker of glomerular filtration, and, hence, renal function. However, transporter-mediated secretion also contributes to its renal clearance, albeit to a lesser degree. Inhibition of these transporters causes transient serum creatinine elevation, which can be mistaken as impaired renal function.
Mechanistic models of creatinine kinetics within physiologically-based framework were developed, with or without consideration of bidirectional transport mechanism of organic anion transporter (OCT)2. Performance of these models were assessed by predicting creatinine-drug interactions with 10 inhibitors of renal transporters in subjects with normal renal function.
The dynamic nature of models provides most advanced framework for evaluating interplay between multiple processes in creatinine renal disposition. Expansion of the creatinine models into chronic kidney disease population will also be illustrated
describe mechanisms involved in creatinine renal disposition
describe the roles of renal transporters in creatinine-drug interactions
describe how physiologically-based creatinine models can be applied to specific populations