The influence of 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate on gliclazide pharmacokinetics and glucose levels in a rat model of diabetes.
The aim of this study was to investigate the pharmacokinetics and glucose-lowering activity of gliclazide alone and in combination with the bile acid salt, sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate (MKC), in a rat model of type I diabetes. Eighty male Wistar rats were divided into eight groups (n=10). Four groups were treated with alloxan (30 mg/kg) to induce diabetes. One group of healthy and one group of diabetic rats were administered gliclazide (20 mg/kg), MKC (4 mg/kg) or a combination of gliclazide (20 mg/kg) and MKC (4 mg/kg). One group of healthy and one group of diabetic rats were used as controls. Blood samples were collected from the tail vein 6 hours post-dose and the plasma was analyzed for glucose concentrations. It was found that gliclazide bioavailability was increased in healthy rats when coadministered with MKC, but there was no difference in glucose levels. Gliclazide bioavailability was much lower in diabetic rats and was not altered by MKC. However, the hypoglycemic effect of the combination of gliclazide and MKC was significantly greater in diabetic rats than that of gliclazide alone. It was demonstrated that the combination of MKC and gliclazide produced a significant hypoglycemic effect in a rat model of Type I diabetes. As gliclazide alone does not have a hypoglycemic effect on Type I diabetic rats, it can be concluded that gliclazide potentiates hypoglycemic effect of MKC in Type I diabetic rats.
Mikov
Momir
M
School of Pharmacy, University of Otago, Dunedin, New Zealand. momir.mikov@stonebow.otago.ac.nz
Al-Salami
Hani
H
Golocorbin-Kon
Svetlana
S
Skrbic
Ranko
R
Raskovic
Aleksandar
A
Fawcett
J Paul
JP
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005907:Gliclazide / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
C520227:3alpha,7alpha-dihydroxy-12-oxo-5beta-cholanate; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D002635:Chenodeoxycholic Acid; D005907:Gliclazide