PMID- 35989252 OWN - NLM STAT- MEDLINE DCOM- 20221202 LR - 20230126 IS - 2160-7648 (Electronic) IS - 2160-763X (Linking) VI - 11 IP - 12 DP - 2022 Dec TI - Bioequivalence of China- and Germany-Manufactured Metformin Extended-Release Tablets Under Fed and Fasted Conditions in Healthy Volunteers: A Randomized, Open-Label, 2-Way Crossover Study. PG - 1430-1439 LID - 10.1002/cpdd.1158 [doi] AB - We compared the bioequivalence, pharmacokinetics, and safety of metformin extended-release (MXR) tablets manufactured by Merck Pharmaceuticals Manufacturing (Jiangsu) Co., Ltd (Nantong, China) and Merck KGaA (Darmstadt, Germany) after a single oral dose under fasted/fed conditions. In this open-label phase 1 study, 54 healthy volunteers (fasted, n = 38; fed, n = 16) were randomly assigned to receive one 500-mg MXR tablet that was manufactured by Merck Pharmaceuticals Manufacturing (Jiangsu) Co. or Merck KGaA. Respectively, the mean terminal half-life was 7.5 and 6.8 hours in the fasted group, and 6.7 and 9.1 hours in the fed group. Median times to maximum observed concentration were 3 and 4 hours (fasted group) and 6 hours (both products, fed group). No significant differences were observed in the metformin plasma concentration-time curve (AUC) from time 0 to the last sampling time and maximum observed concentration between products. Geometric least square mean ratios for maximum observed concentration, AUC from time 0 to the last sampling time, and AUC from time 0 to infinity were nearly 100%; the corresponding 90%CIs for bioequivalence were within 80% to 125%. Diarrhea (26.4%), abdominal pain (5.7%), and nausea (3.8%) were the most common adverse events (AEs); AEs were mild. The mean AUC from time 0 to infinity (test and reference) was substantially increased by approximately 45% in the fed condition (equivalent to a 1.5-fold dose increase); this means food increased net systemic availability but had no impact on AE incidence. This was considered in the study design, which included MXR administration with evening meals. MXR tablets were bioequivalent under fasted/fed conditions and were safe and well tolerated. CI - (c) 2022, The American College of Clinical Pharmacology. FAU - Hu, Chaoying AU - Hu C AD - Department of Pharmacy, Phase I Clinical Trial Center, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital of Capital Medical University, Beijing, China. FAU - Pei, Tong AU - Pei T AD - Department of Pharmacy, Phase I Clinical Trial Center, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital of Capital Medical University, Beijing, China. FAU - Li, Dandan AU - Li D AD - Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd, Beijing, China. FAU - Zhou, Dongli AU - Zhou D AD - Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd, Beijing, China. FAU - Zhang, Lan AU - Zhang L AD - Department of Pharmacy, Phase I Clinical Trial Center, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital of Capital Medical University, Beijing, China. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20220821 PL - United States TA - Clin Pharmacol Drug Dev JT - Clinical pharmacology in drug development JID - 101572899 RN - 9100L32L2N (Metformin) RN - 0 (Tablets) SB - IM MH - Humans MH - Cross-Over Studies MH - Therapeutic Equivalency MH - *Metformin/pharmacokinetics MH - Area Under Curve MH - Tablets MH - China OTO - NOTNLM OT - bioequivalence OT - extended-release tablets OT - metformin OT - pharmacokinetics EDAT- 2022/08/22 06:00 MHDA- 2022/12/03 06:00 CRDT- 2022/08/21 22:16 PHST- 2022/04/15 00:00 [received] PHST- 2022/07/26 00:00 [accepted] PHST- 2022/08/22 06:00 [pubmed] PHST- 2022/12/03 06:00 [medline] PHST- 2022/08/21 22:16 [entrez] AID - 10.1002/cpdd.1158 [doi] PST - ppublish SO - Clin Pharmacol Drug Dev. 2022 Dec;11(12):1430-1439. doi: 10.1002/cpdd.1158. Epub 2022 Aug 21.