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Pharmacokinetics and Pharmacodynamics of Canagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor, in Subjects With Type 2 Diabetes Mellitus.
- Source :
-
Journal of Clinical Pharmacology . Jun2013, Vol. 53 Issue 6, p601-610. 10p. - Publication Year :
- 2013
-
Abstract
- This study characterized single- and multiple-dose pharmacokinetics of canagliflozin and its O-glucuronide metabolites (M5 and M7) and pharmacodynamics (renal threshold for glucose [RTG], urinary glucose excretion [UGE0-24h], and 24-hour mean plasma glucose [MPG0-24h]) of canagliflozin in subjects with type 2 diabetes. Thirty-six randomized subjects received canagliflozin 50, 100, or 300 mg/day or placebo for 7 days. On Days 1 and 7, area under the plasma concentration-time curve and maximum observed plasma concentration (Cmax) for canagliflozin and its metabolites increased dose-dependently. Half-life and time at which Cmax was observed were dose-independent. Systemic molar M5 exposure was half that of canagliflozin; M7 exposure was similar to canagliflozin. Steady-state plasma canagliflozin concentrations were reached by Day 4 in all active treatment groups. Pharmacodynamic effects were dose- and exposure-dependent. All canagliflozin doses decreased RTG, increased UGE0-24h, and reduced MPG0-24h versus placebo on Days 1 and 7. On Day 7, placebo-subtracted least-squares mean decreases in MPG0-24h ranged from 42-57 mg/dL with canagliflozin treatment. Adverse events (AEs) were balanced between treatments; no treatment-related serious AEs, AE-related discontinuations, or clinically meaningful adverse changes in routine safety evaluations occurred. The observed pharmacokinetic/pharmacodynamic profile of canagliflozin in subjects with type 2 diabetes supports a once-daily dosing regimen. [ABSTRACT FROM AUTHOR]
- Subjects :
- *SULFUR compounds
*ANALYSIS of covariance
*CONFIDENCE intervals
*GLYCOSIDES
*MATHEMATICAL statistics
*MEDICAL cooperation
*TYPE 2 diabetes
*REGRESSION analysis
*RESEARCH
*RESEARCH funding
*PARAMETERS (Statistics)
*RANDOMIZED controlled trials
*BLIND experiment
*DATA analysis software
*DESCRIPTIVE statistics
*THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 00912700
- Volume :
- 53
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 87622505
- Full Text :
- https://doi.org/10.1002/jcph.88