Exploring the Clinical Pharmacokinetics of Sitagliptin in Healthy and Diseased Populations: A Systematic Critical...

Sitagliptin is an incretin enhancer used for treating type 2 diabetes mellitus. This review examined the pharmacokinetics (PK) of sitagliptin in healthy and diseased subjects.

Articles related to sitagliptin PK were obtained by searching Google Scholar, PubMed, Cochrane Library, and ScienceDirect. In total, 24 clinical studies encompassing plasma concentration-time profile data after oral and intravenous (IV) administration of sitagliptin were included.

Sitagliptin displays a linear PK profile in healthy subjects as area under the concentration-time curves from zero to infinity (AUC0-inf); the maximum plasma concentration (Cmax) increases with dose. Its AUC0-inf after IV administration (3692.5 ± 504.9 ng·h/mL) and oral dosing (3217.8 ± 496.9 ng·h/mL) indicates an oral bioavailability of ∼87%. Its renal clearance is significantly reduced in patients with moderate hepatic impairment compared with that in healthy subjects (clinically insignificant owing to sitagliptin's wide therapeutic index and predominant renal elimination; dose adjustment is generally not required). Its Cmax is 162.93 ± 37.16 and 181.75 ± 33.44 ng/mL in fasting and fed states, respectively, representing a 1.12-fold increase with food intake (clinically insignificant). Sitagliptin AUC0-inf is 3.5-fold greater in patients with chronic kidney disease than in healthy subjects. Sitagliptin coadministration with gemfibrozil increases its exposure (Cmax increases from 282.9 ± 18.9 to 344.1 ± 14.5 ng/mL; AUC0-inf increases from 3621 ± 222.5 to 5574 ± 611.5 ng·h/mL). Moreover, dorzagliatin does not alter sitagliptin PK parameters.

This review summarizes the available PK data on sitagliptin from published studies in healthy and diseased subjects. These data may be useful for developing physiologically based PK models and may provide additional information to support clinicians in optimizing sitagliptin dosing in patient populations.