Oral antidiabetic drugs: bioavailability assessment of fixed-dose combination tablets of pioglitazone and metformin. Effect of body weight, gender, and race on systemic exposures of each drug.
Bioavailability of pioglitazone and metformin, in 2 dose strengths, given either as a fixed-dose combination tablet or as coadministration of commercial tablets (coad), was studied in young healthy subjects in 2 separate studies. In study I (n = 63), single oral doses of 15-mg pioglitazone/500-mg metformin fixed-dose combination tablets or equivalent doses of commercial tablets were administered, in a fasting state, in an open-label, randomized, crossover study with a 7-day washout period between treatments. Study II (n = 61) was similar in design to study I, except the 15/850-mg fixed-dose combination tablet and coad treatments were evaluated. Least squares mean (fixed-dose combination/coad) ratios and 90% confidence intervals of the ratios for the 15/500-mg dose strength for the maximum observed serum concentration (Cmax) and area under the serum concentration-time curve from time 0 to infinity (AUC(infinity)) were 0.95 (0.86-1.05) and 1.02 (0.98-1.08), respectively, for pioglitazone and 0.99 (0.95-1.03) and 1.03 (0.98-1.08), respectively, for metformin. Bioequivalency for pioglitazone and metformin between fixed-dose combination tablets and coad treatments was met for both strengths of fixed-dose combination tablets. In a post hoc meta-analysis of combined data from the 2 studies (n = 124), there was considerable overlapping in AUC(infinity) values between gender and race (Caucasians, Blacks, and Hispanics), making neither gender- nor racial-based dosing of pioglitazone or metformin necessary.
Karim
Aziz
A
Takeda Global Research & Development Center, Inc, 475 Half Day Road, Lincolnshire, IL 60069, USA. akarim@tgrd.com
Slater
Margaret
M
Bradford
Dawn
D
Schwartz
Lisa
L
Zhao
Zhen
Z
Cao
Charlie
C
Laurent
Aziz
A
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D044383:Black People; D001835:Body Weight; D004338:Drug Combinations; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016018:Least-Squares Analysis; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D000077205:Pioglitazone; D012737:Sex Factors; D013810:Therapeutic Equivalency; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D044465:White People
D004338:Drug Combinations; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D008687:Metformin; D000077205:Pioglitazone