Al-Salami Hani, Butt Grant, Tucker Ian, Fawcett Paul J, Golocorbin-Kon Svetlana, Mikov Ivan, Mikov Momir
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Eur J Drug Metab Pharmacokinet. 2009 Jan-Mar;34(1):43-50. doi: 10.1007/BF03191383.
The aim is to investigate the influence of the antidiabetic drug gliclazide on the ileal permeation of the semisynthetic bile acid, MKC, in tissues from healthy and diabetic rats. Sixteen Wistar rats (350 +/- 50 g) were randomly allocated into four groups (4 rats per group, 8 chambers per rat, i.e., n=32) two of which were made diabetic (given alloxan i.v. 30 mg/kg). Group 1 was used to measure the permeation of MKC (50 microg/ml) alone (control) while group 2 to measure MKC permeation in the presence of gliclazide (200 microg/ml). The diabetic groups 3 (gliclazide) and 4 (MKC+gliclazide) were treated in the same way. Rats were sacrificed and tissues were mounted into the Ussing chamber for the measurement of MKC mucosal to serosal (absorptive) and serosal to mucosal (secretory) fluxes. In healthy tissues, gliclazide reduced MKC absorptive flux (p < 0.01) and increased its secretory flux (p < 0.01). In diabetic tissues, gliclazide had no effect on either the absorptive or the secretory fluxes of MKC. The lack of effect of gliclazide on MKC permeation in diabetic tissues suggests the absence or suppressed drug transporters. Furthermore, gliclazide inhibition of MKC absorptive flux and induction of MKC secretory flux in healthy tissues may result from the selective inhibition of an efflux drug transporter.
目的是研究抗糖尿病药物格列齐特对半合成胆汁酸MKC在健康大鼠和糖尿病大鼠组织中回肠渗透的影响。将16只Wistar大鼠（350±50 g）随机分为四组（每组4只大鼠，每只大鼠8个腔室，即n = 32），其中两组制成糖尿病模型（静脉注射30 mg/kg四氧嘧啶）。第1组用于单独测量MKC（50μg/ml）的渗透（对照），而第2组用于测量在格列齐特（200μg/ml）存在下MKC的渗透。糖尿病组3（格列齐特）和4（MKC +格列齐特）以相同方式处理。处死大鼠并将组织安装在Ussing腔室中以测量MKC从粘膜到浆膜（吸收性）和从浆膜到粘膜（分泌性）的通量。在健康组织中，格列齐特降低了MKC的吸收通量（p <0.01）并增加了其分泌通量（p <0.01）。在糖尿病组织中，格列齐特对MKC的吸收或分泌通量均无影响。格列齐特对糖尿病组织中MKC渗透缺乏作用表明药物转运体不存在或受到抑制。此外，格列齐特在健康组织中对MKC吸收通量的抑制和对MKC分泌通量的诱导可能是由于对一种外排药物转运体的选择性抑制。
