The role of organic cation transporter 2 inhibitor cimetidine, experimental diabetes mellitus and metformin on gabapentin pharmacokinetics in rats.

PURPOSE: We investigated the influence of diabetes mellitus (DM), glycemic control with insulin, cimetidine (Oct2 inhibitor) and metformin (Oct2 substrate) on the kinetic disposition of GAB in rats. MAIN METHODS: Male Wistar rats were divided in five groups and all animals received an oral dose of 50 mg/kg GAB: (vehicle + GAB), cimetidine + GAB (single dose of cimetidine [100 mg/kg] intraperitoneally 1 h before GAB), metformin + GAB (single dose of metformin 100 mg/kg by gavage concomitantly with GAB), DM + GAB (single dose of 40 mg/kg streptozotocin (STZ) intravenously) and DM + GAB + insulin (single dose 40 mg/kg STZ intravenously and 2 IU insulin twice daily for 15 days). Pharmacokinetic analysis was based on plasma and urine data concentrations. KEY FINDINGS: No differences in pharmacokinetic parameters were observed between vehicle + GAB × cimetidine + GAB and vehicle + GAB × metformin + GAB groups. Diabetes increased the fraction of GAB excreted unchanged in urine (vehicle + GAB: 0.48 [0.38-0.58]; DM + GAB: 0.83 [0.62-1.04]; DM + GAB + insulin: 0.88 [0.77-0.93]) (mean [95% confidence interval]) without any changes in GAB exposure. Insulin treated diabetic animals showed higher renal clearance compared to control (vehicle + GAB: 0.25 [0.18-0.30] L/h·kg; DM + GAB + insulin: 0.55 [0.45-1.43] L/h·kg), which was attributed to the diabetes-induced glomerular hyperfiltration. SIGNIFICANCE: Glomerular filtration is the main mechanism of renal excretion of GAB without significant contribution of Oct2 active transport.

Midriasis farmacológica en conejos inducida por antagonistas de histamina / Pharmacologic midriasis induced by histamine antagonist in rabits

El propósito de este trabajo es determinar el efecto de antagonistas de histamina sobre el esfínter pupilar y la superficie ocular en conejos pigmentados. Para ello se realizó un estudio experimental, longitudinal y comparativo. Se estudiaron 50 ojos de 25 conejos, divididos en 4 grupos: I cimetidina, II clorfenamina, III tropicamida al 1 por ciento y IV fenilefrina al 10 por ciento + ciclopentolato al 1 por ciento. Como resultado, se demostró que la combinación de cimetidina y tropicamida al 1 por ciento produce pérdida de reflejo pupilar a los 5 minutos, midriasisi máxima a los 15 minutos, delcinando a los 45 minutos de su aplicacion. Se concluye que la combinación de cimetidina y tropicamida al 1 por ciento en forma tópica, induce pérdida del reflejo pupilar y midriasis a corto plazo desapareciendo rápidamente el afecto

An improved high performance liquid chromatographic method for determination of cimetidine and its major metabolite in plasma.

An improved HPLC method for the measurement of cimetidine and its major metabolite-cimetidine sulfoxide-is described. The mobile phase was a mixture of methanol-ammonium phosphate (20:80), and methanol was used to elute the drug avoiding the use of acetonitrile, a very hazardous solvent. A device has been developed to wash simultaneously ten or more cartridges and to reduce the time of analysis. With this procedure a plasma sample could be analyzed in less than 30 min. The limit of detection was 0.125 micrograms/ml for cimetidine and 1.00 micrograms/ml for cimetidine sulfoxide. The absolute recovery for cimetidine was 83% and 40% for its major metabolite; is greater than that reported by previous studies. The proposed method is rapid, accurate and precise, and it should be useful for clinical, bioavailability and pharmacokinetic studies of cimetidine.