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�й�ҩѧ��־ 2012, Vol. 47 Issue (19) :1565-1569    DOI:
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ZHANG Dan��YANG Man��HAN Jing��WANG Xiao-lin��ZHANG Li-na��ZHANG Ya-nan��XIAO Xue��DU Ai-hua�� LIU Man��WANG Zhen-long��WANG Tao��LIU Hui-chen
Department of Clinical Pharmacology�� Aerospace Center Hospital�� Beijing 100049�� China

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Abstract�� OBJECTIVE To reevaluate the bioequivalence of marked metformin hydrochloride enteric-coated tablets.METHODSUsing method 2 described in the appendix X D and apparatus 1 described in the appendix X C in Chinese Pharmacopoeia��edition 2010����the in vitro release of metformin hydrochloride enteric-coated tablets from different pharmaceutical factories ��A��B��C��and D�� was investigated. The contents were measured by utlraviolet ��UV��spectroscopy.Generic tablets from factory A and D were chosen to be test 1 and test 2 preparations��with the innovative metformin hydrochloride tablets ��Glucophage�� as the reference preparation. In a randomized��three-way crossover study��21 healthy male volunteers were given a single oral dose of test 1��test 2 and reference preparations containing 500 mg of metformin hydrochloride. Plasma concentrations of metformin were determined by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated. The bioequivalence between test 1 and reference preparation��test 2 and reference preparation��and the bioequivalence between the two test preparations were evaluated.RESULTS The in vitro release of metformin hydrochloride enteric-coated tablets from factory B��C and D met the standard of Chinese Pharmacopoeia��the supplement edition of 2010�� while that of the tablets from factory A did not.Metformin hydrochloride enteric-coated tablets from factory A and D were chosen to be test 1 and test 2 preparations��respectively. The F0-t and F0-�� were ��72.8��9.7�� % and ��73.2��10.0�� % for test 1 preparation��and ��45.5��16.2�� % and ��46.2��16.0�� % for test 2 preparation��respectively. It was failed to conclude that test 1 and reference preparation were bioinequivalent. Test 2 and reference preparation were bioinequivalent��and the two test preparations were also bioinequivalent.CONCLUSION The bioinequivalence risk of metformin hydrochloride enteric-coated tablets is high. For metformin hydrochloride enteric-coated tablets��not only conducting pre-marketing bioequivalence study with proper reference preparation��but also enhancing post-marketing surveillance and reevaluation of bioequivalence are very important for maintaining the consistency of drugs quality��
Keywords�� metformin hydrochloride,   enteric-coated tablet,   in vitro release,   bioequivalence,   post-marketing reevaluation,   bioinequivalence risk     
�ո�����: 2012-06-09;
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�ŵ�, ����, ������ .�������˫�ҳ���Ƭ���к����������Ч��������[J]  �й�ҩѧ��־, 2012,V47(19): 1565-1569
ZHANG Dan, YANG Man, HAN Jing etc .Post-Marketing Reevaluation of Bioequivalence of Metformin Hydrochloride Enteric-Coated Tablets[J]  Chinese Pharmaceutical Journal, 2012,V47(19): 1565-1569
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[1] BAILEY C J��TURNER R C. Metfor min [J]. N Engl J Med��1996��334��9���� 574-579��
[2] KIRPICHNIKOV D��MCFARLANE S I��SOWERS J R. Metfor min�� An update ��J��. Ann Intern Med��2002 137��1���� 25-33��
[3] QIANG G F��HAN J��YANG M��et al. Post-marketing bioarailability monitoring and reevaluation of generic drugs[J]. Chin Pharm J���й�ҩѧ��־����2011��46��16���� 1290-1292��
[4] Ch. P. Vol��Suppl�����й�ҩ��2010���.����������S/OL��. ��2011-04-29��. http��//www. chp. org. cn/export/sites/chp/resource/history01/20110429xz06. pdf
[5] ZHANG D��WANG G C��HUANG J Q��et al. LC-MS/MS deter mination of metfor min in human plasma[J]. Chin J Pharm Anal��ҩ�������־����2011��31��2���� 317-321��
[6] MARATHE P H��ARNOLD M E��MEEKER J��et al. Pharmacokinetics and bioavailability of a metfor min/glyburide tablet ad ministered alone and with food [J]. J Clin Pharmacol��2000��40��12 Pt 2���� 1494-1502��
[7] KARIM A��SLATER M��BRADFORD D��et al. Oral antidiabetic drugs�� Effect of food on absorption of pioglitazone and metfor min from a fixed-dose combination tablet [J]. J Clin Pharmacol��2007��47��1���� 48-55��
[8] IWAO K��KAWAI R T��ODA M��et al. Physicochemical interactions of metfor min hydrochloride and glibenclamide with several health foods [J]. Yakugaku Zasshi��2008��128��9���� 1341-1345��
[9] HE Y L��FLANNERY B��CAMPESTRINI J��et al. Effect of food on the pharmacokinetics of a vildagliptin/metfor min ��50/1 000 mg�� fixed-dose combination tablet in healthy volunteers [J]. Curr Med Res Opin��2008��24��6���� 1703-1709.
[10] GRAHAM G G��PUNT J��ARORA M��et al. Clinical pharmacokinetics of metfor min [J]. Clin Pharmacokinet��2011�� 50��2����81-98��
[11] BLUME H H��SCHUG B S. The biopharmaceutics classification system ��BCS���� Class III drugs-better candidates for BA/BE waiver [J]. Eur J Pharm Sci��1999��9��2���� 117-121��
[12] CHENG C L��YU L X��LEE H L��et al. Biowaiver extension potential to BCS Class III high solubility-low permeability drugs�� bridging evidence for metfor min immediate-release tablet [J]. Eur J Pharm Sci��2004��22��4���� 297-304��
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[2] ʩ���� ���� ���ļ� ��ȫӢ .����������͡��Ĥ��Ƭ�������Ч���о�[J]. �й�ҩѧ��־, 2012,47(5): 367-370
[3] ������ ����Ƽ ���ж� ʩТ�� ������.����Ī˾�����������ڵ������Ч������[J]. �й�ҩѧ��־, 2012,47(4): 296-302
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[8] �º��� ������ ���� �ι�Ҷ.���������θ����������ƻ��ͽ��ҵ��Ʊ��͹��տ���[J]. �й�ҩѧ��־, 2011,46(8): 605-609
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[13] ������ ��ȫӢ ���ļ� ���� ����.Һ��ɫ��-�������׷��о���ɳ̹��Ƭ�������Ч�Լ�����ҩ��ѧ[J]. �й�ҩѧ��־, 2011,46(14): 1108-1111
[14] ������ ������ �Ų��� ¦��ʯ ����Т.���޲����������������˫�ҵ������Ч���о�[J]. �й�ҩѧ��־, 2011,46(11): 860-865
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