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Dipeptidyl peptidase-IV, MK-0431, incretins, antihyperglycemic therapy, www.clinicaltrials.gov, NCT00696826
Sitagliptin is a highly selective dipeptidyl peptidase-4 inhibitor for the treatment of patients with type 2 diabetes. Sitagliptin is primarily excreted by renal elimination as unchanged drug, with only a small percentage (~16%) undergoing hepatic metabolism.
The primary purpose of this study was to evaluate the influence of moderate hepatic insufficiency on the pharmacokinetics of sitagliptin.
In an open-label study, a single 100 -mg oral dose of sitagliptin was administered to 10 male or female patients with moderate hepatic insufficiency (Child-Pugh’s scores ranged from 7 to 9) and 10 healthy control subjects matched to each patient for race, gender, age (± 5 yrs) and body mass index (BMI kg/m2 ± 5%). After administration of each dose, blood and urine samples were collected to assess sitagliptin pharmacokinetics.
The mean AUC0 -? and Cmax for sitagliptin were numerically, but not significantly (p>0.050), higher in patients with moderate hepatic insufficiency compared with healthy matched control subjects by 21% and 13%, respectively. These slight differences were also not considered to be clinically meaningful. Moderate hepatic insufficiency had no statistically significant effect on the Tmax , apparent terminal t1/2, fraction of the oral dose excreted into urine (fe,0-¥) and renal clearance (ClR) (p>0.100) of sitagliptin. Sitagliptin was generally well tolerated by both patients and subjects; all adverse experiences were transient and rated as mild in intensity.
Moderate hepatic insufficiency has no clinically meaningful effect on the pharmacokinetics of sitagliptin
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