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Pharmacokinetics of Repaglinide in Healthy Caucasian and Japanese Subjects
Author(s) -
Thomsen M. S.,
Chassard D.,
Evène E.,
Nielsen K. K.,
Jørgensen M.
Publication year - 2003
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270002239702
Subject(s) - pharmacokinetics , medicine , repaglinide , crossover study , body mass index , area under the curve , dosing , pharmacodynamics , gastroenterology , metformin , placebo , insulin , alternative medicine , pathology
The objective of this study was to investigate the pharmacokinetics of three different single doses (0.5, 1.0, and 2.0 mg) of repaglinide in healthy Caucasian and Japanese subjects. In this single‐center, open‐label, randomized, three‐period crossover study, 27 healthy male subjects (15 Caucasian and 12 Japanese) each received three different single doses of repaglinide (0.5, 1.0, and 2.0 mg) at consecutive 24‐hour intervals. Pharmacokinetic profiles, including area under the curve (AUC 0‐t ), maximum serum concentration (C max ), time to C max (t max ), and half‐life (t 1/2 ), were determined for each dose of repaglinide. The relative change in blood glucose level (RC 1h ) and area under the blood glucose curve (AUGC 0–1 ) at 1 hour after dose were also measured. After oral dosing, both C max and AUC 0‐t increased linearly with dose within the 0.5‐ to 2.0‐mg dose range, regardless of ethnic group. Both C max and AUC 0‐t were significantly higher in Japanese subjects than in Caucasian subjects. At each dose of repaglinide, C max and AUC were statistically significantly higher in Japanese than in Caucasian subjects ( p = 0.0038 and 0.023, respectively). Discrepancies in body weight and body mass index (BMI) between Caucasian and Japanese subjects could not explain the between‐group differences in C max or AUC 0‐t . Statistically significant differences in pharmacodynamic parameters (RC 1h and AUGC 0–1 ) were found between ethnic groups ( p < 0.0001), the difference being more pronounced for RC 1h than AUGC 0–1 . At a dose of 2.0 mg, the mean decrease in RC 1h was 41% for Japanese subjects and 24% for Caucasian subjects. Hypoglycemic reactions were more common at the highest dose (2.0 mg), where they were observed more frequently in Japanese (7 cases) than in Caucasian subjects (4 cases). It was concluded that higher serum levels of repaglinide and greater reductions in blood glucose levels are found in Japanese than in Caucasian subjects following a single oral dose of repaglinide within the 0.5‐ to 2.0‐mg dose range. Repaglinide is well tolerated in both ethnic groups. The results indicate that glycemic control targets may be achieved at lower doses within the recommended range (0.5–4.0 mg/meal) when repaglinide is used to treat Japanese patients in comparison to Caucasian patients.