Effect of Renal Insufficiency on the Pharmacokinetics of Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor

• Published in: Diabetes care Vol. 30; no. 7; pp. 1862 - 1864
• Main Authors: Bergman, Arthur J, Cote, Josee, Yi, Bingming, Marbury, Thomas, Swan, Suzanne K, Smith, William, Gottesdiener, Keith, Wagner, John, Herman, Gary A
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.2007
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Care and treatment; Complications and side effects; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Drug therapy; Endocrinopathies; Enzyme Inhibitors - pharmacokinetics; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Health aspects; Hemodialysis; Humans; Hypoglycemic Agents - pharmacokinetics; Inhibitor drugs; Kidney diseases; Kidney failure; Male; Mass spectrometry; Medical sciences; Middle Aged; Pharmacokinetics; Pharmacology; Proteases; Pyrazines - pharmacokinetics; Renal Insufficiency - etiology; Renal Insufficiency - physiopathology; Sitagliptin Phosphate; Studies; Triazoles - pharmacokinetics; Type 2 diabetes; Urine; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Vital signs; United States; Dipeptidyl-peptidase IV; Kidney disease; Urinary system disease; Nutrition; Enzyme; Mimetic; Enzyme inhibitor; Metabolic diseases; Sitagliptin; Peptidases; Hypoglycemic agent; Analog; Renal failure; Hydrolases; Pharmacokinetics; Endocrinology
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc06-2545

Pharmacokinetic analysis Sitagliptin was measured in plasma, urine, and dialysate samples by mass spectrometry detection following specialized high-performance liquid chromatography with an internal standard (3). The recommended sitagliptin dosage adjustments are as follows: no adjustment for patients with mild RI (creatinine clearance 50-80 ml/ min), a twofold decrease in the clinical dose of 100 mg q.d. (i.e., 50 mg q.d.) for patients with moderate RI (creatinine clearance 30-50 ml/min) (approximate serum creatinine levels >1.7 and ^3.0 mg/dl for men and > 1.5 and ^2.5 mg/dl for women), and a fourfold decrease in the clinical dose (25 mg q.d.) for patients with severe RI (creatinine clearance <30 ml/min) or ESRD (approximate serum creatinine levels >3.0 mg/dl for men, >2.5 mg/dl for women, or on dialysis).