Nitric oxide synthase activity and endogenous inhibitors in rats recovered from allergic encephalomyelitis

We have previously reported that in comparison with normal rats, the presence of experimental allergic encephalomyelitis (EAE) leads to decreased endogenous inhibitory activity (EIA) of Ca2+-dependent nitric oxide synthase (NOS) in both brain and serum, and increased expression of protein 3-nitrotyrosine (NT) in brain. In this work we show that animals recovered from the clinical signs of EAE are not different from controls in terms of either brain NOS activity, EIA of NOS, or NT expression. These results suggest that parallel to the reversal of the disease symptoms, a normalization of the production of nitric oxide and related species occurs.

Measurement of plasma verapamil levels by high-performance liquid chromatography

1. We have developed an alternative procedure for the measurement of verapamil levels in human plasma by reverse-phase high performance liquid chromatography with fluorimetric detection. 2. Prior to assay, plasma is submitted to a double extraction procedure, using first n-heptane in alkaline medium and then an acid phosphate buffer. Flecainide, a compound not related to verapamil, is used as internal standard. Mean recoveries of 70 and 63 per cent were obtained for verapamil and flecainide, respectively. 3. The sensitivity (5 ng/ml), reproducibility (inter-assay per cent CV = 1.7-8.7; intra-assay per cent CV = 2-4) and high recovery during sample clean-up make this method useful for the quantitation of verapamil in therapeutic monitoring and pharmacokinetic studies. 4. The method is illustrated with the pharmacokinetic results obtained for 14 healthy male volunteers who received a single 240 mg dose of the commercially available tablets of Dilacoron Retard 240 mg. The mean values for the area under the curve from 0 to 24 h (AUC[0-24]), maximum achieved concentration (Cmax) and time to achieve the maximum concentration (Tmax) were 863 ng h-1 ml-1, 112 ng/ml and 4 h, respectively

Biovailability of four pharmaceutical formulations of metronidazole tested on normal healthy volunteers

1. Single doses of four metronidazole formulations (the unmarketed Trichomol, 200 mg, 200 mg, 400 mg, 500 mg, and the commercially available Flagyl, 400 mg) were administered to 14 healthy adult male volunteers in order to determine their pharmacokinetic profiles. 2. Plasma metronidazole concentrations were measured by high pressure liquid chromatography. The results were plotted against time and the curves obtained were used to calculate pharmacokinetic parameters ( area under the curves, maximun achieved concentration and time at which it occurred, elimination constant, and half-life). 3. Trichomol formulations of 200 mg and 500 mg significantly differed from the 400 mg formulation with respect to area under the curve and maximum concentration. Trichomol 400 mg and Flagyl 400 mg showed no significant differences in maximum concentration or area under the curve. No differences were observed in half-life or time of appearance of maximum concentration among formulations. 4. Good correlations occurred between maximum concentration, area under the curve and amount of metronidazole ingested, indicating a linear pharmacokinetic profile. 5. We conclude that Trichomol 400 mg proved to be bioequivalent to the commercially available reference Flagyl 400 mg according to U.S. Food and Drug Adminsitration requirements

Inhibitory effect of enalapril on serum aldosterone in essential hypertension

El objetivo del presente estudio fue evaluar en pacientes hipertensos esenciales, el efecto inhibitorio agudo y crónico del maleato de enalapril sobre la aldosterona plasmática. Diez pacientes con hipertensión arterial esencial leve y moderada (7 varones y 3 mujeres), con edades comprendidas entre 15 y 60 años, recibieron, luego de un período placebo de 28 días, 20mg de maleato de enalapril en una sola toma diaria. Durante el período placebo y a las 24, 48 y 72h de iníciado el tratamiento se determinó la actividad renínica plasmática (ARP) y los níveles de angiotensina II (AII) y aldosterona plasmática (A) por radioinmunoensayo, midiéndose asimismo la presión arterial media (PAM) utilizando un equipo automático de presión arterial (Critikon, Dynamap). Se comprobó un descenso significativo de la PAM de 120,6ñ4mmHg a 104,4ñ3, 102,6ñ2 y 100,5ñ1mmHg a las 24,48 y 72h, respectivamente (p<0,01). La ARP se incrementó de 0,68ñ0,6ng/ml/h a 9,33ñ2; 9,67ñ2 y 10,5ñ2ng/ml/h (p<0,05) y la AII descendió de 70,8ñ18pg/ml a 35,1ñ5; 27,6ñ3 y 25ñ4pg/ml (p<0,05)en el mismo período. La A descendió de 141,9ñ8 a 94,7ñ5pg/ml a las 24h (p<0,05), para retornar a las 48 y 72h a los niveles previos al tratamiento (106,7ñ6 y 118,5ñ7pg/ml). Ocho pacientes continuaron recibiendo enalapril 20mg/día durante un período de 6 meses al cabo del cual se determinó nuevamente AII y A previo y a las 2, 4 y 6h luego de la dosis diaria de enalapril. Se comprobó un descenso de la AII de 38,7ñ9 a 29ñ11pg/ml a las 2h (p<0,05), a 21ñ5pg/ml a las 4h (p<0,02) y a 17,5ñ4pg/ml a las 6h (p<0,01) de administrada la dosis de enalapril. La A descendió también de 170,14 a 106,3ñ8; 98,7ñ7 y 89,3ñ5pg/ml a las 2,4 y 6h de recibida la droga (p<0,01). En 7 de los 8 pacientes estudiados, se obtuvo una correlación individual entre AII y A que osciló en un rango de r entre 0,69 y la unidad. Se concluye que el enalapril mantiene el efecto inhibitorio sobre la enzima convertidora en el largo plazo al persistir reducidos los niveles de AII a los 6 meses de tratamiento. La tendencia a la recuperación de los niveles de aldosterona observados a las 48 y 72h y su posterior retorno a losvalores iniciales se debería a unasupersensibilidad del receptor de AII, aunque no podría descartarse la participación de la ACTH