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PIII‐60
Author(s) -
Bergman A. J.,
Cote J.,
Yi B.,
Wang A. Q.,
Zeng W.,
Chen L.,
Marbury T.,
Swan S.,
Smith W.,
Gottesdiener K. M.,
Wagner J. A.,
Herman G. A.
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.2005.12.268
Subject(s) - medicine , pharmacokinetics , cmax , renal function , hemodialysis , urology , end stage renal disease , sitagliptin , dialysis , creatinine , gastroenterology , kidney disease , urinalysis , diabetes mellitus , type 2 diabetes , pharmacology , endocrinology , urinary system
BACKGROUND/AIMS This study was conducted to evaluate the influence of renal insufficiency (RI) on the pharmacokinetics (PK) of sitagliptin (SIT), a selective DPP‐IV inhibitor in Phase III development for the treatment of type 2 diabetes. METHODS 6 patients/subjects in each of the following groups: mild RI (creatinine clearance (CrCl) = 50 to 80 mL/min), moderate RI (CrCl = 30 to 50 mL/min), severe RI (CrCl < 30 mL/min) and healthy subjects (CrCl > 80 mL/min). Each group received a single oral 50‐mg dose of SIT. End‐stage renal disease (ESRD) patients received 2 single oral 50‐mg doses (hemodialysis 4‐hr or 48‐hr postdose). SIT PK in RI patients was compared to concurrent and historical control subjects. Less than 2‐fold increases in AUC 0‐∞ were not considered clinically meaningful changes. RESULTS SIT AUC 0‐∞ was approximately inversely related to CrCl. Renal clearance (Cl R ) was approximately proportional to CrCl. AUC 0‐∞ increased less than 2‐fold for CrCl > 50 mL/min. AUC 0‐∞ was 1.6, 2.3, 3.8 and 4.5‐fold higher in mild RI, moderate RI, severe RI and ESRD patients, respectively, compared to healthy subjects. C max was 1.4, 1.4, 1.8 and 1.4 higher in mild moderate and severe RI and ESRD, respectively. Dialysis removed ∼13.5% of the dose. SIT was well tolerated in all groups. CONCLUSIONS Mild RI patients do not require dose‐adjustment. To obtain an exposure of SIT similar to patients without renal insufficiency, moderate RI, and severe RI and ESRD patients should receive ½ and ¼ of the usual SIT dose, respectively. Clinical Pharmacology & Therapeutics (2005) 79 , P75–P75; doi: 10.1016/j.clpt.2005.12.268