Glibenclamide-pregnenolone derivative has greater hypoglycemic effects and biodistribution than glibenclamide-OH in alloxan-rats.
OBJECTIVE
The present study was designed to investigate the activity of two glibenclamide derivatives on glucose concentration. An additional aim was to identify the biodistribution of glibenclamide derivatives in different organs in a diabetic animal model.


METHODS
The effects of two glibenclamide derivatives on glucose concentration were evaluated in a diabetic animal model. In addition, glibenclamide derivatives were bound to Tc-99m using radioimmunoassay methods. To evaluate the pharmacokinetics of the glibenclamide derivatives over time (15, 30, 45 and 60 min) the Tc-99m-glibenclamide conjugates were used.


RESULTS
The results showed that glibenclamide-pregnenolone had greater hypoglycemic activity than glibenclamide or glibenclamide-OH. The data also showed that the biodistribution of Tc-99m-glibenclamide-OH in all organs was less than that of the Tc-99m-glibenclamide-pregnenolone derivative.


CONCLUSIONS
The glibenclamide-pregnenolone derivative had greater hypoglycemic effects and its biodistribution was wider than glibenclamide-OH. The data suggest that the steroid nucleus may be important to the hypoglycemic activity of the glibenclamide-pregnenolone derivative and this could be related to the degree of lipophilicity induced by the steroid nucleus in the chemical structure of glibenclamide-pregnenolone.
Laboratorio de Investigacion en Ciencias Biologicas y Farmacoqimica, Facultad de Ciencias Quimico-Biologicas, Universidad Autonoma de Campeche, Av. Agustin Melgar, Col Buenavista C.P.24039 Campeche Cam., Mexico. lauro_1999@yahoo.com
Lauro
L
Figueroa-Valverde
Francisco
F
Diaz-Cedillo
Maria
M
Lopez-Ramos
Elodia
E
Garcia-Cervera
Eduardo
E
Pool-Gomez
Carlos
C
Cardena-Arredondo
Graciela
G
Ancona-Leon
D000496:Alloxan; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004338:Drug Combinations; D005260:Female; D005905:Glyburide / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000493:pharmacokinetics; D008687:Metformin / Q000627:therapeutic use; D011284:Pregnenolone / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D001786:Blood Glucose; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D000496:Alloxan; D011284:Pregnenolone; D008687:Metformin; D005905:Glyburide