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No pharmacokinetic interaction between ipragliflozin and sitagliptin, pioglitazone, or glimepiride in healthy subjects
Author(s) -
Smulders R. A.,
Zhang W.,
Veltkamp S. A.,
Dijk J.,
Krauwinkel W. J. J.,
Keirns J.,
Kadokura T.
Publication year - 2012
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2012.01624.x
Subject(s) - glimepiride , sitagliptin , pioglitazone , pharmacokinetics , medicine , pharmacology , urology , crossover study , type 2 diabetes , endocrinology , diabetes mellitus , placebo , alternative medicine , pathology
Aims To investigate the effect of ipragliflozin on the pharmacokinetics of sitagliptin, pioglitazone or glimepiride and vice versa in healthy subjects. Methods Three trials with an open‐label, randomized, two‐way crossover design were conducted in healthy subjects. Ipragliflozin 150 mg, sitagliptin 100 mg, pioglitazone 30 mg or glimepiride 1–2 mg were administered alone or in combination. Primary endpoints were the area under the curve from the time of dosing to infinity ( AUC inf ) and the maximum observed plasma concentration (C max ) of each drug. Results Multiple doses of ipragliflozin did not change the AUC inf and C max of a single dose of sitagliptin, pioglitazone or glimepiride. All geometric mean ratios and 90% CIs for AUC inf and C max , with and without ipragliflozin, were within the predefined range of 80–125% ( AUC inf : sitagliptin 100.1 [96.9–103.5], pioglitazone 101.7 [96.6–107.0], glimepiride 105.1 [101.3–109.0], and C max : sitagliptin 92.4 [82.8–103.1], pioglitazone 98.6 [87.7–110.8], glimepiride 110.0 [101.9–118.8]). Similarly, multiple doses of sitagliptin, pioglitazone or glimepiride did not change the pharmacokinetics of a single dose of ipragliflozin ( AUC inf : 95.0 [93.4–103.1], 100.0 [98.1–102.0], 99.1 [96.6–101.6]; and C max : 96.5 [90.4–103.1], 93.5 [86.3–101.2], 97.3 [89.2–106.2]). Ipragliflozin either alone or in combination with any of the three glucose‐lowering drugs was well tolerated in healthy subjects. Conclusion Ipragliflozin did not affect the pharmacokinetics of sitagliptin, pioglitazone or glimepiride and vice versa, suggesting that no dose‐adjustments are likely to be required when ipragliflozin is given in combination with other glucose‐lowering drugs in patients with type 2 diabetes mellitus.