Gliclazide reduces MKC intestinal transport in healthy but not diabetic rats.
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.
Al-Salami
Hani
H
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Butt
Grant
G
Tucker
Ian
I
Fawcett
Paul J
PJ
Golocorbin-Kon
Svetlana
S
Mikov
Ivan
I
Mikov
Momir
M
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005907:Gliclazide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards
D007004:Hypoglycemic Agents; C530580:sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate; D002635:Chenodeoxycholic Acid; D005907:Gliclazide