Résumé
The study was conducted to find the involvement of Nitric Oxide (NO) using L-arginine, a NO precursor and NG-methyl L-arginine a nitric oxide synthase inhibitor on tolbutamide activity in normal rabbits. L-arginine (25-300 mg/kg, body weight, oral) produced transient and dose dependent hypoglycaemia. When combined with tolbutamide (40 mg/kg, oral) it produced early and prolonged action. The effect of tolbutamide was blocked by NG-methyl L-arginine (5 mg/kg, body weight, oral). The results confirm the involvement of NO in tolbutamide activity and the possibility of using L-arginine as a supplement to antidiabetic drugs in blood glucose control.
Sujets)
Animaux , Arginine/pharmacologie , Glycémie/effets des médicaments et des substances chimiques , Femelle , Hypoglycémie/sang , Hypoglycémiants/pharmacologie , Mâle , Monoxyde d'azote/physiologie , Lapins , Tolbutamide/pharmacologieRésumé
Acute treatment of rabbits with pargyline (50 mg/kg, ip, 30 min before tolbutamide) significantly increased the elimination half life and AUC0-->infinity of tolbutamide resulting in prolonged hypoglycaemia. Similar treatment also prolonged the half life of antipyrine which is used as model drug to indicate hepatic microsomal enzyme activity in vivo confirming that pargyline treatment delayed the elimination of tolbutamide in rabbits by inhibiting its hepatic metabolism.
Sujets)
Animaux , Phénazone/pharmacocinétique , Glycémie/analyse , Interactions médicamenteuses , Femelle , Période , Hypoglycémie/induit chimiquement , Injections péritoneales , Mâle , Microsomes du foie/effets des médicaments et des substances chimiques , Pargyline/administration et posologie , Lapins , Tolbutamide/administration et posologieRésumé
The influence of ranitidine on the hypoglycaemic activity of glibenclamide and tolbutamide was studied in rabbits. Ranitidine treatment (15 mg/kg, po, twice daily for one week) enhanced the hypoglycaemic activity of glibenclamide (40 micrograms/kg, po) while it has not altered either the hypoglycaemic activity or pharmacokinetics of tolbutamide (40 mg/kg, po) in rabbits.