RESUMEN
The physicochemical stability and the compatibility between N-acetylcysteine (1 g/5 ml), betamethasone (4 mg/1 ml) and netilmicin (100 mg/1 ml) were studied at room temperature (25+/-2 degrees C) over 1 h. During this study, drug concentrations were measured using three separate HPLC methods with UV detection at t=0, 5, 10, 20, 30, and 60 min. The pH of the mixture was determined. Degradation products of the drugs were assayed using HPLC. This study demonstrates the stability and compatibility of the mixture over 1 h at room temperature. The pinkish non-remnant coloration observed when pouring N-acetylcysteine into a recipient has no effect on the stability of the drug.
Asunto(s)
Acetilcisteína/química , Betametasona/química , Netilmicina/química , Acetilcisteína/análisis , Aerosoles/análisis , Aerosoles/química , Betametasona/análisis , Cromatografía Líquida de Alta Presión , Composición de Medicamentos , Incompatibilidad de Medicamentos , Estabilidad de Medicamentos , Concentración de Iones de Hidrógeno , Netilmicina/análisis , Factores de TiempoRESUMEN
It has been previously demonstrated that the mixture of Cu, Au and Ag impaired significantly the clinical and biochemical disorders induced by adjuvant arthritis in the rat. The efficiency of this mixture and of each component was tested on the same animal model. Treated rats were injected daily with either 22.8 micrograms of copper gluconate, 0.2 micrograms of gold thioglucose, 6.8 micrograms of silver proteinate or the blended solution over a period of 29 d. The treatment with the one component solutions was found to have a little or no effect on the plasma levels of fibrinogen, haptoglobin, ceruloplasmin, prostaglandin E2, thromboxane B2, total proteins, Zn, Cu, Mn, Se, Co and Ni, and no significant decrease was observed in the paw oedema resulting from the Freund's adjuvant injection. The treatment with the mixture had a significant preventive effect. Therefore it seems that the administration of low doses of each of the three trace elements have no anti-rheumatic property in the rat. The results indicate an enhanced effect of the metal mixture in the model studied.
Asunto(s)
Artritis Experimental/tratamiento farmacológico , Aurotioglucosa/uso terapéutico , Gluconatos/uso terapéutico , Proteínas de Plata/uso terapéutico , Animales , Aurotioglucosa/administración & dosificación , Proteínas Sanguíneas/metabolismo , Ceruloplasmina/metabolismo , Gluconatos/administración & dosificación , Masculino , Metales/sangre , Ratas , Ratas Wistar , Proteínas de Plata/administración & dosificación , Tromboxano B2/metabolismoRESUMEN
Metabolism of two broad spectrum quinolones in advanced preclinical development-tosufloxacin and BMY 43748-was compared in hepatocyte cultures derived from rat, dog, monkey and humans. The drugs were added at the first medium renewal and incubated for 4 or 24 hr in serum-free medium. Metabolites were analysed by HPLC. Marked species differences were found in both the metabolic rates and pathways of the two quinolones. BMY 43748 was found to be more actively metabolized than tosufloxacin in cultured hepatocytes from the three animal species. Human hepatocytes were totally ineffective, thereby indicating that they were metabolically different from monkey cells. Comparison with available in vivo data demonstrated a good but not perfect qualitative in vivo/in vitro correlation.
RESUMEN
The efficacy of a drug containing three heavy metals together has been tested in adjuvant-induced arthritic rats. Treated rats were injected with 22.8 micrograms copper gluconate, 0.2 microgram gold thioglucose and 6.8 micrograms silver proteinate each day during a period of 29 days. The drug treatment was found to diminish the increases in plasma levels of haptoglobin, ceruloplasmin, PGE2, 6-keto-PGF1 alpha and copper, the decrease in the iron plasma level induced by Freund's adjuvant and the paw swelling. No effect was seen on the plasma levels of TXB2, Zn, Se, Mn and Ni. Therefore the simultaneous administration of low doses of gold, copper and silver had a real anti-rheumatic property in this model. These results should be of interest for the long-term treatment of arthritis.