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�й�ҩѧ��־ 2012, Vol. 47 Issue (23) :1915-1919    DOI:
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JIANG Bin�� ZHANG Hao-bing�� LIU Cong-shan�� TAO Yi

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ժҪ Ŀ�� �۲�3�ֱ���������ҩ��������򡢷ұ������������򣩵�3�ֻ����������ᡢ���ͺ�1%�����Ƚ��Ļ���������С�����ڵ�ҩ��ѧ������������Ӧ�������ܽ�Ⱥ��������öȵ�����ԡ����� ����ĥ���Ʊ��������򡢷ұ������������������ᡢ���ͺ�1%�����Ƚ��Ļ������������ռ��ͣ���ÿ��45��54ֻС��1�οڷ�1�������ı���������ҩ�����Һ����������������ѡ��100 mg��kg-1�⣬����ұ�����ͷ��������Ϊ50 mg��kg-1�����ڸ�ҩ��0.25��24 h�IJ�ͬ���ʱ��ȡѪ���ø�ЧҺ��ɫ�׷��ⶨѪҩŨ�ȣ���DAS�������3�ֱ���������ҩ���ҩ��ѧ��������� С��ڷ�3�ֱ���������ҩ�������ᡢ���ͺ�1%�����Ƚ��������󣬰��������ƽ������ʱ��(MRT)�ֱ�Ϊ(3.91��0.29)��(3.70��0.09)��(1.59��0.14) h����Ũ��(��max)�ֱ�Ϊ(0.66��0.08)��(0.29��0.05)��(0.34��0.09) mg��L-1��ҩ��Ũ��-ʱ�����������(AUC)�ֱ�Ϊ(3.19��0.40)��(1.25��0.09)��(0.50��0.05) mg��L��h-1������������ö�F(�������ͻ��������AUC��1%�����Ƚ���������AUC֮�ȣ���ͬ)�ֱ�Ϊ6.38��2.50���ұ������MRT�ֱ�Ϊ(5.72��0.14)��(4.83��0.38) ��(3.85��0.25)h����max�ֱ�Ϊ(0.70��0.11)��(0.20��0.05)��(0.12��0.03) mg��L-1�� AUC�ֱ�Ϊ(5.02��0.73)��(1.08��0.21)��(0.52��0.07) mg��h��L-1��F�ֱ�Ϊ9.65��2.08�����������MRT�ֱ�Ϊ(5.71��0.37)��(4.59��0.39)��(3.34��0.20)h����max�ֱ�Ϊ(0.93��0.14)��(0.58��0.09)��(0.41��0.09) mg��L-1�� AUC�ֱ�Ϊ(6.90��0.73)��(3.33��0.39)��(1.94��0.55) mg��h��L-1��F�ֱ�Ϊ3.57��1.72������ С��һ�οڷ��������򡢷ұ��������������2���������������1%�����Ƚ���������ȣ���ҩ��ѧ�������Ը��ƣ��ӳ���MRT���������max��ͬʱ������AUC��F������3�ֱ���������ҩ����3�ֽ����е��ܽ��������С�����ڵ�MRT����max��AUC����������ء�
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Abstract�� OBJECTIVE To determine the pharmacokinetics of three benzimidazoles (albendazole�� fenbendazole and flubendazole) suspended in three different media [oleic acid�� soybean oil or 1% tragacanth (served as control)] in mice�� and observe the correlation of those pharmacokinetic parameters with the solubilities of the three benzimidazoles in corresponding medium. METHODS Albendazole�� fenbendazole and flubendazole suspened in oleic acid�� soybean oil or 1% tragacanth were prepared by ball grinding mill. Groups of 45-54 mice were administered orally with one of aforementioned benzimidazole suspensions at a single dose of 100 mg��kg-1 (albendazole) or 50 mg��kg-1 (fenbendazole and flubendazole). Subgroups with 5-6 mice in each group were bled at varying intervals within 24 h. Plasma was then separated from heparin-anticoagulated blood�� and evaluated for the presence of the drug by high performance liquid chromatography (HPLC). Pharmacokinetic parameters of each drug were calculated using DAS (Drug AnaLyze System). RESULTS After oral administration of three benzimidazoles suspended in oleic acid�� soybean oil or 1% tragacanth�� the pharmacokinetic parameters of each drug were described as follows�� albendazole�� the MRT (average retention time) were (3.91��0.29)�� (3.70��0.09) and (1.59��0.14) h�� ��max (maximum concentration) were (0.66��0.08)�� (0.29��0.05) and (0.34��0.09) mg��L-1�� AUC (area under the concentration-time curve) were (3.19��0.40)�� (1.25��0.09) and (0.50��0.05) mg��L��h-1�� F (relative bioavailability�� the AUC compared with that of 1% tragacanth group) were 6.38 and 2.50�� fenbendazole�� the MRT were (5.72��0.14)�� (4.83��0.38) and (3.85��0.25) h�� ��max were( 0.70��0.11)�� (0.20��0.05) and (0.12��0.03) mg��L-1�� AUC were (5.02��0.73)�� (1.08��0.21) and (0.52��0.07) mg��h��L-1�� F were 9.65 and 2.08�� flubendazole�� the MRT were (5.71��0.37)�� (4.59��0.39) and (3.34��0.20) h�� ��max were (0.93��0.14)�� (0.58��0.09) and (0.41��0.09) mg��L-1�� AUC were (6.90��0.73)�� (3.33��0.39) and (1.94��0.55) mg��L��h-1�� F were 3.57 and 1.72. CONCLUSION After oral administration to mice�� the major pharmacokinetic parameters of the three benzimidazoles suspended in oleic acid and soybean oil show significant improvement compared to those of the same drugs suspended in 1% tragacanth�� which manifest as prolongation of MRT�� and increase of ��max�� AUC as well as F. The solubilities of the three benzimidazoles in three different media were on the whole positive correlative to their MRT�� ��max�� AUC and F in mice.
Keywords�� benzimidazole,   albendazole,   fenbendazole,   oleic acid,   soybean oil,   suspension,   pharmacokinetics,   bioavailability      
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JIANG Bin, ZHANG Hao-Bing, LIU Cong-Shan etc .Pharmacokinetics of Three Benzimidazoles Suspended in Oleic Acid�� Soybean Oil or 1% Tragacanth�� and Administered Orally to Mice at A Single Dose [J]  Chinese Pharmaceutical Journal, 2012,V47(23): 1915-1919
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