Previous studies report the effects of combination treatment without significant buy VRT752271 increases in the risk of AEs such as hypoglycemia [32, 33]. A recent study reports the efficacy on glucose fluctuation when added to DPP-4 inhibitors and administered to patients receiving ongoing sulfonylurea-based therapy . Glimepiride is
one of the most commonly used sulfonylureas due to its convenient once-daily dosing regimen and tissue selectivity. Although some potential YH25448 supplier interactions with glimepiride have been predicted, such as some drugs that are metabolized by CYP2C9 (e.g. phenytoin, diclofenac, naproxen) and protein-binding drugs (e.g. sulfonamides, probenecid, β-blocking agents), no clinically significant drug interactions have been reported PX-478 mouse . Theoretically, gemigliptin could also be administered with glimepiride,
but there are no reported interactions between these drugs. Therefore, this study was conducted to assess the pharmacokinetic interactions and tolerability of gemigliptin and glimepiride when administered in combination to healthy volunteers. It is unlikely that pharmacokinetic interactions occur between these two drugs because it is known that gemigliptin demonstrates no significant effects on cytochromes, operates via different metabolic pathways, and demonstrates no strong protein-binding characteristics, but clinically confirming this lack of interactions is important given the fact that combination therapy might help some patients. In this study, glimepiride demonstrated no pharmacokinetic effects on steady-state gemigliptin, nor did gemigliptin affect the pharmacokinetics of single-dose glimepiride. Also, the time to maximum concentration and the half-life of the combination therapies were comparable to each monotherapy. In the case of gemigliptin, the half-life was somewhat shorter than previously reported by multiple-dose studies (16.6–20.1 h); we determined a mean
until value of 8.77 h for monotherapy and 10.45 h for combination therapy. However, as mentioned in the previous studies, differences in sampling time affected this value; in this study, blood sampling was performed ≤24 h after the last dose, but previous studies obtained blood samples ≤72 h after the last dose. In fact, day 1 of a previous study using 24 h sampling to calculate half-life showed similar (7.4–9.3 h) results to our study . Therefore, terminal half-life calculated in this study could be somewhat biased. Because the pharmacokinetic profile of each drug is well known, and we should consider the safety concerns of blood sampling from healthy volunteers, we planned to obtain the minimum number of samples required to evaluate pharmacokinetic interactions. Therefore, blood sampling was limited to the dosing interval (24 h).