Involvement of nitric oxide (NO) in hypoglycaemic activity of tolbutamide.

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.

Experiencia clínica con un inhibidor de la alfa glucosidasa (acarbosa) en el tratamiento de la diabetes no insulinodependiente: estudio multicéntrico / Multicentric study on the effect of an alpha glucosidase inhibitor in the treatment of non insulin dependent diabetes

Diabetic patients received acarbose, 150 mg/day durign four weeks and this dose was increased to 300 mg/day durign 3 months. Afterwards, patients were followed for a period of 12 weeks without acarbose. Fasting and post-prandial blood glucose and glycosilated hemoglobin were measured sequentially durign the study. Results: Eighty five patients were recruited for the study but 64 complied with the treatment protocol. The age of these patients was 56 ñ 8.8 years old, their diabetes duration was 7.8 ñ 8.8 years and their body mass index was 27.6 ñ 3.6 kg/m². During acarbose treatment, glycosilated hemoglobin decreased from 8.36 ñ 1.33 to 7.71 + 1.7 percent (p < 0.001), fasting blood glucose decreased from 173 ñ 48 to 159 ñ 59 mg/dl (p < 0.03) and post-prandial blood glucose decreased from 254 ñ 80 to 241 ñ mg/dl (NS). After discontinuing acarbose glycosilated hemoglobin and blood glucose levels returned to basal levels. Body weight and blood pressure did not change during the treatment period. Fifty nine patients bad gastrointestinal symptoms (meteorism, flatulence and abdominal distention) that were mild in 59 percent and moderate in 39 percent. Episodes of hypoglycemia were not observed. Conclusions: Acarbose, associated to sylphonylureas is an effective drug to reduce blood glucose and glycosilated hemoglobin levels in patients with non insulin dependent diabetes

Biologically active principles isolated from Salacia oblonga wall.

From the petroleum ether extract of the root bark of Salacia Oblonga wall, two biologically active fractions have been isolated by column and thin layer chromatography. The methanol eluted fraction of the extract absorbed on a column of silica gel at a concentration of 50 micrograms/ml showed 100 percent cytotoxicity on Ehrlich ascites tumour cells. The chloroform eluted fraction of the pet. ether extract and a fluorescent compound separated from it by TLC demonstrated about 60% and 76% hypoglycemic potency of an equal dose of tolbutamide (250 mg/kg) in albino rats. The results indicate the therapeutic importance of S. Oblonga wall.

Hypoglycemic effect of Ocimum sanctum leaf extract in normal and streptozotocin diabetic rats.

Oral administration of alcoholic extract of leaves of O. sanctum led to marked lowering of blood sugar level in normal, glucose fed hyperglycemic and streptozotocin induced diabetic rats. Further the extract potentiated the action of exogenous insulin in normal rats. The activity of the extract was 91.55 and 70.43% of that of tolbutamide in normal and diabetic rats respectively.

Effect of allopurinol on tolbutamide pharmacokinatics and hypoglycaemic activity in rabbits

The effect of allopurinol on pharmacokinetic parameters and hypoglycemic activity of tolbutamide was assessed in fasted rabbits. Pretreatment of animals with allopurinol [30 mg/kg orally] 2 hours before tolbutamide injection [50 mg/kg i.v.] resulted in a significant increase in plasma tolbutamide levels compared to those of rabbits received tolbutamide alone. The plasma half life [t1/2] of tolbutamide increased from 6.60 to 12.83 hours by allopurinol pretreatment. The hypoglycemic activity of tolbutamide was also significantly enhanced in rabbits received allopurinol. These results suggested the importance of tolbutamide dosage adjustment when allopurinol is given concurrently

Bioequivalencia de tabletas comerciales de tolbutamida usando al perro Beagle como modelo animal / Bioequivalence of commercial tolbutamide tablets using the beagle dog as an animal model

El proposito de este estudío fué el de determinar la bioequivalencia de tabletas comerciales de tolbutamida. Se estudio la velocidad de disolución de tolbutamida de 19 tabletas, provenientes de 8 fabricantes, de acuerdo a las especificaciones de la USP XX. La bioequivalencia de 6 productos fué comparada contra el producto innovador Orinase (R) en 12 perros beagle. Las concentraciones plasmáticas de glucosa y tolbutamida se determinaron para tres productos y para los otros cuatro solamente glucosa. Diez productos no pasaron la prueba de disolución y dos de ello s fueron menos biodisponibles que el producto innovador (pV0.05). Sin embargo, otros dos productos que fallaron la prueba de disolución fueron bioequivalentes. Las concentraciones plasmáticas promedio de glucosa fueron significativamente correlacionas con la cantida disuelta a diversos tiempos. En conclusión, este estudio indica que existe alto potencial de presentarse diferencias clínicas en humanos para los productos bioinequivalentes probados en perros