Pharmacokinetics and relative bioavailability of compound metformin hydrochloride and glibenclamide capsule in healthy Chinese volunteers

Abstract

Abstract: AIM: To compare pharmacokinetics and relative bioavailability of metformin and glibenclamide in compound metformin hydrochloride and glibenclamide capsule (CMGC) with the reference preparations metformin tablet (MT) and glibenclamide tabet (GT). METHODS: Twenty male healthy volunteers were enrolled in a randomized two-way crossover design with a single-oral dose study.The plasma metformin and glibenclamide concentrations were determined by high performance liquid chromatography (HPLC) and liquid chromatography-mass spectrography (LC-MS), respectively.Pharmacokinetics parameters were calculated and bioequivalability was analyzed by two one-side t-test. RESULTS: The pharmacokinetics parameters of metformin in CMGC and co-administration of metformin glinbenclamide were as following, respectively:C_max (1.87 ± 0.36 and 1.77 ±0.35) mg·L ^-1;Tmax (1.7 ±0.6 and 1.8 ±0.5) h;AUC_0-∞(8.13 ±1.32 and 8.62 ±1.47) mg·L ^-1·h ^-1, while those of glinbenclamide were as following, respectively: C_max (129.2 ±51.4 and 123.9 ±50.7) μg·L ^-1;T_max(2.3 ±0.7 and 2.6 ±0.9) h;AUC_0-∞ (0.690 ±0.228 and 0.632 ±0.211) mg·L ^-1·h ^-1.Relative bioavailability of metformin and glibenclamide in CGMC were 95.0 % ±11.5 % and 109.6 %±8.8 %, respectively. CONCLUSION: The main components of CMGC, metformin and glibenclamide, are bioequivalent to the reference tablets, MT and GT.

Key words: metformin, glibenclamide, pharmacokinetics, bioavailability CLC

CLC Number:

R969

YIN Xiao-Xing, ZHANG Yi-Di, DING Li, SHEN Jian-Ping, LI Li-Min, QIU Jun. Pharmacokinetics and relative bioavailability of compound metformin hydrochloride and glibenclamide capsule in healthy Chinese volunteers[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(6): 623-627.

References

1 Melander A, Bitzen PO, Faber O, Groop L.Sulphonylurea antidiabetic drugs.An update of their clinical pharmacology and rational therapeutic use[J].Drugs, 1989;37(1):58-72
2 Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE. Metabolic effects of metformin in non-insulin-dependent diabetes mellitus[J].N Engl J Med, 1995;333(9):550-4
3 Lupi R, Marchetti P, Giannarelli R, Coppelli A, Tellini C, Del Guerra S, et al.Effects of glibenclamide and metformin (alone or in combination) on insulin release from isolated human pancreatic islets[J].Acta Diabetol, 1997;34(1):46-8
4 Erle G, Lovise S, Stocchiero C, Lora L, Coppini A, Marchetti P, et al.A comparison of preconstituted, fixed combinations of low-dose glyburide plus metformin versus high-dose glyburide alone in the treatment of type 2 diabetic patients[J].Acta Diabetol, 1999;36(1-2):61-5
5 Bokhari SU, Gopal UM, DuckworthWC.Beneficial effects of a glyburide metformin combination preparation in type 2 diabetes mellitus[J].Am JMed Sci, 2003;325(2):66-9
6 Hermann LS, Schersté n B, Bitzé n PO, Kjellstrom T, Lindgarde F, Melander A.Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations.A double-blind controlled study[J].Diabetes Care, 1994;17(10):1100-9
7 VasudevanM, Ravi J, Ravisankar S, Suresh B.Ion-pair liquid chromatography technique for the estimation of metformin in its multicomponent dosage forms[J].J Pharm Biomed Anal, 2001; 25(1):77-84
8 Zarghi A, Foroutan SM, Shafaati A, Khoddam A.Rapid determination of metformin in human plasma using ion-pair HPLC [J].J Pharm Biomed Anal, 2003;31(1):197-200
9 Khatri J, Qassim S, Abed O, Abraham B, Al-Lami A, Masood S.A novel extractionless HPLC fluorescence method for the determination of glyburide in the human plasma:application to a bioequivalence study [J].J Pharm Pharmaceut Sci, 2001;4(2):201-6
10 Hsieh S, Selinger K.High-throughput bioananlytical method using automated sample preparton and liquid chromatographyatmospheric pressure ionspray mass spectrometry for quantitative determination of gybenclamide in human serum[J].J Chromatogr B Analyt Technol Biomed Lif Sci, 2002;772(2):347-56
11 Scheen AJ.Clinical pharmacokinetics of metformin[J].Clin Pharmacokinet, 1996;30(5):359-71
12 Groop LC, Luzi L, De Fronzo RA, Melander A.Hyperglycemia and absorption of sulfonylurea drugs[J].Lancet, 1989;2(8655):129-30
13 Whalin-Boll E, Almer LO, Melander A.Bioavailability, kinetics and effects of glipizide in type 2-diabetics[J].Clin Pharmacokinet, 1982;7(4):363-72

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