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Pharmacokinetics and pharmacodynamics of the DPP‐4 inhibitor, LAF237, in patients with type 2 diabetes
Author(s) -
He Y. L.,
Balch A.,
Campestrini J.,
Rivere G. J.,
Serra D.,
Prasad P.,
LiguerosSaylan M.
Publication year - 2005
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.2004.12.104
Subject(s) - cmax , pharmacodynamics , medicine , pharmacokinetics , type 2 diabetes , glycemic , placebo , dosing , insulin , diabetes mellitus , pharmacology , endocrinology , alternative medicine , pathology
Background LAF237 is a selective DPP‐4 inhibitor under development as an anti‐diabetic agents. The objective of this study was to assess the PK/PD in patients with type 2 diabetes (T2D). Methods Thirteen patients were enrolled and 12 completed this study. Each patient was randomly assigned to receive one of the four treatments for 28 days: placebo (PBO), 10, 25, or 100 mg of LAF237 bid. Blood samples were collected on day 28 for measurement of LAF237, DPP‐4, GLP‐1, glucose and insulin over 16 hr while standard mixed meals were served. Results LAF237 was rapidly absorbed and the C max was observed during 1~2 hr. Both C max and AUC increased dose proportionally. More than 90% DPP‐4 inhibition was achieved after all doses, while the duration of >90% DPP‐4 inhibition increased with dose. LAF237 100 mg bid increased GLP‐1 levels >2 fold compared to placebo. Mean glucose levels over 14 hr were significantly reduced by 10% and 19%, respectively, at 25 mg and 100 mg bid compared to PBO (p<0.05). LAF237 at 10 mg bid did not show effect on glucose. Since insulin levels were maintained while glycemic levels were reduced, the results suggest that insulin secretion was increased relative to the observed glucose levels. Conclusions LAF237 was well tolerated at dose up to 100 mg bid in patients with T2D. LAF237 was rapidly absorbed and significantly inhibited DPP‐4 activity. Glucose levels were significantly reduced after 25 and 100 mg bid dosing, indicating that LAF237 is a promising new approach for the treatment of patients with T2D. Clinical Pharmacology & Therapeutics (2005) 77 , P56–P56; doi: 10.1016/j.clpt.2004.12.104