title: Dose-proportionality of a final market image sitagliptin formulation, an oral dipeptidyl peptidase-4 inhibitor, in healthy volunteers.
abstract: Sitagliptin is a highly selective orally active dipeptidyl peptidase-4 inhibitor recently approved in the United States for the treatment of type 2 diabetes. Ten healthy subjects received single oral doses of 25, 50, 100, 200 and 400 mg final market image tablets in five separate treatment periods in randomized fashion to assess dose proportionality. Blood (up to 72 h post-dose) and urine (up to 24 h post-dose) samples for sitagliptin pharmacokinetic analysis were collected at pre-specified times following administration of sitagliptin. Dose-proportionality of AUC(0-infinity), C(max) and C(24 h) was assessed using a power-law model. The results of this study indicate that plasma AUC(0-infinity) increased in a dose-proportional manner over the 25-400 mg dose range. Over the same dose range, plasma C(max) increased in a greater than dose-proportional manner and C(24 h) increased in a modestly less than dose proportional manner. No clinically meaningful differences in T(max) or apparent t(1/2) were noted across the dose range. Differences in the percentage of the sitagliptin dose excreted unchanged in urine (72.5% pooled across doses) and renal clearance (344 ml/min pooled across doses) were not statistically significant. Sitagliptin was generally well tolerated at all the doses evaluated.
authors.affiliation: Merck & Co Inc., Whitehouse Station, NJ 07065, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Bergman
authors.forename: Goutam C
authors.initials: GC
authors.lastname: Mistry
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Luo
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: Julie
authors.initials: J
authors.lastname: Stone
authors.forename: Amy
authors.initials: A
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zeng
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Stacy
authors.initials: S
authors.lastname: Dilzer
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lasseter
authors.forename: Gary A
authors.initials: GA
authors.lastname: Herman
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
authors.forename: Rajesh
authors.initials: R
authors.lastname: Krishna
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000068900:Sitagliptin Phosphate; D013607:Tablets; D053719:Tandem Mass Spectrometry; D014230:Triazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D004791:Enzyme Inhibitors; D011719:Pyrazines; D013607:Tablets; D014230:Triazoles; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate