Premium
PII‐49
Author(s) -
Stevens C.,
Bergman A. J.,
Liu Q.,
Luo W.,
Wang A. Q.,
Zeng W.,
Lasseter K. C.,
Dilzer S.,
Wagner J. A.,
Herman G. A.,
Migoya E.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.174
Subject(s) - sitagliptin , pharmacokinetics , cmax , dipeptidyl peptidase 4 inhibitor , medicine , sitagliptin phosphate , pharmacology , dipeptidyl peptidase 4 , urine , oral administration , endocrinology , gastroenterology , type 2 diabetes , diabetes mellitus
BACKGROUND This study was conducted to evaluate the influence of hepatic insufficiency (HI) on the pharmacokinetics of MK‐0431 (sitagliptin), an orally active, highly selective DPP‐IV inhibitor currently in Phase III development for the treatment of patients with type 2 diabetes. METHODS This was an open‐label study during which a single 100‐mg oral dose of sitagliptin was administered to 10 patients with moderate HI (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 (±5%). Following each dose, blood and urine samples were collected to assess sitagliptin pharmacokinetics. Prespecified bounds for non‐clinical significance for the AUC were[0.5, 2.00]. RESULTS Mean sitagliptin plasma AUC 0‐∞ and C max were approximately 21% and 13% higher, respectively, than matched control subjects; both parameters fell within the prespecified bounds. Moderate HI had no statistically significant effect on T max , apparent terminal t 1/2 , fraction of the oral dose excreted into urine (f e,0‐∞ ) and renal clearance (p>0.100) of sitagliptin. Sitagliptin was generally well tolerated by patients and subjects. CONCLUSIONS Moderate HI has no clinically meaningful effect on the pharmacokinetics of sitagliptin and no dosage adjustment will be necessary for patients with moderate HI. Clinical Pharmacology & Therapeutics (2005) 79 , P49–P49; doi: 10.1016/j.clpt.2005.12.174