Sign Out
Pharmacology: Pharmacokinetics: After oral administration of a 100-mg dose to healthy subjects, Sitagliptin was rapidly absorbed, with peak plasma concentrations (median Tmax) occurring 1 to 4 hours post-dose. Plasma AUC of Sitagliptin increased in a dose-proportional manner. Plasma AUC of Sitagliptin increased approximately 14% following 100-mg doses at steady-state compared to the first dose. The pharmacokinetics of Sitagliptin were generally similar in healthy subjects and in patients with type 2 diabetes.
Absorption: The absolute bioavailability of Sitagliptin is approximately 87%. Since coadministration of a high-fat meal with Sitagliptin had no effect on the pharmacokinetics, Sitagliptin may be administered with or without food.
Distribution: The mean volume of distribution at steady state following a single 100-mg intravenous dose of Sitagliptin to healthy subjects is approximately 198 litres. The fraction of Sitagliptin reversibly bound to plasma proteins is low (38%).
Elimination: Sitagliptin is eliminated in faeces (13%) or urine (87%) within one week of dosing. The apparent terminal t½ following a 100-mg oral dose of Sitagliptin was approximately 12.4 hours and renal clearance was approximately 350 mL/min.
Special populations: Gender: No dosage adjustment is necessary based on gender.
Elderly: No dosage adjustment is required based on age.
Race: No dosage adjustment is required based on race.
Hepatic Insufficiency: No dosage adjustment for Sitagliptin is necessary for patients with mild or moderate hepatic insufficiency. There is no clinical experience in patients with severe hepatic insufficiency.
Renal Insufficiency: Dosage adjustment is needed in renal insufficiency (see Dosage & Administration).
Pediatric Patients: No studies with Sitagliptin have been performed in paediatric patients.
Body Mass Index (BMI): No dosage adjustment is necessary based on BMI.
Toxicology: Animal Toxicology: Acute Toxicity: The approximate LD50 of Sitagliptin given orally to rats is >3000 mg/kg (maximum dose tested). This dose is equivalent to ≥200 times the human exposure based on the recommended daily adult human dose of 100 mg/day. In mice the approximate oral LD50 of Sitagliptin is 4000 mg/kg. This dose is equivalent to >385 times the human exposure based on recommended daily adult human dose of 100 mg/day.
Carcinogenicity: There was an increased incidence of hepatic adenomas and carcinomas in the high-dose males and hepatic carcinomas in the high-dose females. The clinical significance of these findings for humans is unknown.
Mutagenesis: Sitagliptin was not mutagenic or clastogenic in a battery of genetic toxicology studies, including the Ames bacterial assay (microbial mutagenesis test), Chinese hamster ovary cells (CHO cells) chromosome aberration assay, an in vitro cytogenetics assay using CHO cells, an in vitro rat hepatocyte DNA alkaline elution assay (an assay which measures the compound's ability to induce single strand breaks in DNA), and an in vivo micronucleus assay.
