alexa Oral bioavailability and hypoglycaemic activity of tolbutamide cyclodextrin inclusion complexes.
Psychiatry

Psychiatry

Journal of Addiction Research & Therapy

Author(s): Veiga F, Fernandes C, Teixeira F

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Abstract The purpose of the present study was to evaluate the enhancement of tolbutamide (TBM) oral bioavailability and hypoglycaemic activity through complexation with beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD). TBM and its freeze-dried inclusion complexes were administered to rabbits (New zealand breed; n=6), in a dose of 20 mg/kg. TMB plasma levels were measured by HPLC and glucose levels were analysed according to Trinder (Trinder, P., 1969. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann. Clin. Biochem. 6, 24-28). The pure drug attained a maximum of plasma concentration (C(max)) of 18.58+/-3.27 microg/ml at 8.5 h (T(max)), whereas with inclusion complexes, C(max) increased about two times and appeared at ca. 4 h. AUC(0-24) of complexes was about 1.6 times as much as that of the pure drug. Thus, the extent of oral absorption of TBM from inclusion complexes was significantly greater and faster when compared with drug alone. In addition, without cyclodextrins the maximum hypoglycaemic effect (CVG(max)) of TBM (34. 1\%) was observed at 5.6 h (Tg(max)). CVG(max) of TBM/beta-CD and TBM/HP-beta-CD inclusion complexes were 34.1\% (at 6.5 h) and 37.7\% (at 5.1 h), respectively. AAC(0-24) of inclusion complexes was 1.4 times larger than that of pure drug. Hence, the oral administration of complexed TBM not only improved the drug absorption, but also the TBM hypoglycaemic activity.
This article was published in Int J Pharm and referenced in Journal of Addiction Research & Therapy

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