PMID- 20685507 OWN - NLM STAT- MEDLINE DCOM- 20101122 LR - 20141120 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 32 IP - 5 DP - 2010 May TI - Bioequivalence and pharmacokinetic evaluation of two formulations of glimepiride 2 mg: a single-dose, randomized-sequence, open-label, two-way crossover study in healthy Chinese male volunteers. PG - 986-95 LID - 10.1016/j.clinthera.2010.04.016 [doi] AB - BACKGROUND: Glimepiride is an oral sulfonylurea antihyperglycemic agent indicated for the treatment of type 2 diabetes mellitus. Although there are reports in the literature regarding the pharmacokinetic (PK) characteristics of glimepiride, few data of PK parameters are available in a Chinese population; none are available regarding a recently developed generic formulation. OBJECTIVE: To meet the requirements for marketing a new generic product in China, the study was designed to compare the PK properties and bioequivalence of 2-mg tablets of glimepiride: the newly developed generic formulation (test) and a branded formulation (reference) in healthy Chinese male volunteers. METHODS: A single-dose, randomized-sequence, open-label, 2-way crossover study was conducted in fasted healthy Chinese male volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive 1 tablet (2 mg each) of the test or reference formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Plasma samples were collected before study drug administration (baseline) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours after study drug administration. Concentrations in plasma of the parent glimepiride and its M1 metabolite were analyzed with a LC-MS/MS method. The formulations were considered bioequivalent if the 90% CIs for the log-transformed values were within the predetermined equivalence range (70%-143% for C(max) and 80%-125% for AUC), according to the guidelines of the State Food and Drug Administration (SFDA) of China. Tolerability was based on the recording of adverse events (AEs), monitoring vital signs, ECGs, and laboratory tests at baseline and completion of the study. RESULTS: A total of 24 healthy Chinese male volunteers were enrolled and completed the study; however, only the data from 23 subjects were included (mean [SD] age, 23.6 [2.2] years [range, 18.6-26.9 years]; weight, 64.0 [8.4] kg [range, 52.0-82.0 kg]; and height, 172.3 [5.6] cm [range, 164.0-185.0 cm) in the PK and tolerability assessments due to a violation of the protocol. For parent glimepiride, the 90% CIs for the ratios of Cmax, AUC(0-t), and AUC(0-infinity) were 93.83% to 115.19%, 90.82% to 102.29%, and 92.22% to 103.78%, respectively. For the M1 metabolite, the 90% CIs were 91.71% to 110.79%, 91.33% to 101.76%, and 89.99% to 99.85%. Both met the predetermined criteria for bioequivalence. Four AEs (17.4%) were reported: hypertriglyceridemia (2 subjects [8.7%]; 1 each receiving the test and reference formulations); increase of red blood cells in urine (1 subject [4.3%] receiving the reference formulation); and hypoglycemia (1 subject [4.3%] receiving the test formulation). The incidence of hypoglycemia was the only AE considered probably related to study drug administration; all others were considered probably not related. All AEs were transient and considered by the investigators to be mild. CONCLUSIONS: In this small study in fasted healthy Chinese male volunteers, a single 2-mg dose of the test formulation met the regulatory criteria to assume bioequivalence to the reference formulation based on the rate and extent of absorption. Both formulations were well tolerated. SFDA Registration No.: 2009L01033. CI - Copyright 2010 Excerpta Medica Inc. All rights reserved. FAU - Liu, Yun AU - Liu Y AD - Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China. FAU - Zhang, Meng-qi AU - Zhang MQ FAU - Zhu, Jian-min AU - Zhu JM FAU - Jia, Jing-ying AU - Jia JY FAU - Liu, Yan-mei AU - Liu YM FAU - Liu, Gang-yi AU - Liu GY FAU - Li, Shuijun AU - Li S FAU - Weng, Li-ping AU - Weng LP FAU - Yu, Chen AU - Yu C LA - eng PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Hypoglycemic Agents) RN - 0 (Sulfonylurea Compounds) RN - 6KY687524K (glimepiride) SB - IM MH - Adolescent MH - Adult MH - Area Under Curve MH - Chemistry, Pharmaceutical MH - China MH - Cross-Over Studies MH - Humans MH - Hypoglycemic Agents/*pharmacokinetics MH - Male MH - Sulfonylurea Compounds/*administration & dosage/*pharmacokinetics MH - Therapeutic Equivalency EDAT- 2010/08/06 06:00 MHDA- 2010/12/14 06:00 CRDT- 2010/08/06 06:00 PHST- 2010/02/12 00:00 [accepted] PHST- 2010/08/06 06:00 [entrez] PHST- 2010/08/06 06:00 [pubmed] PHST- 2010/12/14 06:00 [medline] AID - S0149-2918(10)00140-2 [pii] AID - 10.1016/j.clinthera.2010.04.016 [doi] PST - ppublish SO - Clin Ther. 2010 May;32(5):986-95. doi: 10.1016/j.clinthera.2010.04.016.