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2.
Eur J Pharmacol ; 53(4): 335-42, 1979 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-421731

RESUMEN

Dantrolene sodium is a muscle relaxant used in the treatment of spasticity. It has been shown to interfere with calcium release from the sarcoplasmic reticulum and thus to inhibit excitation--contraction coupling. The effect of dantrolene sodium on the twitch tension of the tibialis anterior muscle of the rat was measured after 2 mg/kg i.v. or 25 mg/kg orally. Plasma concentrations were estimated at maximum twitch depression and during recovery from the block. In a separate series of experiments the half-life of labelled dantrolene sodium was measured in blood plasma, skeletal muscle and heart muscle of rats. Dantrolene sodium 2 mg/kg i.v. gave a maximal block of approximately 47%, the mean dantrolene sodium concentration was then 5.8 microgram/ml. A half-life for distribution of 1.1 min and an elimination half-life of 31 min after intravenous administration were observed, elimination rate constants in skeletal and heart muscle were comparable. Recovery from the block went much slower, the half-time of the process being approximately 80 min. Dantrolene sodium 25 mg/kg orally gave a maximal block of approximately 38% at a mean plasma concentration of 3.6 microgram/ml after 14 min. The recovery was again very slow. These experiments demonstrated that dantrolene sodium acts according to a two-compartment pharmacokinetic model. There was a discrepancy between duration of effect and plasma concentration of dantrolene sodium in the rat. This suggests that the receptor for dantrolene sodium is not located in the central compartment.


Asunto(s)
Dantroleno/metabolismo , Hidantoínas/metabolismo , Animales , Dantroleno/farmacología , Relación Dosis-Respuesta a Droga , Semivida , Cinética , Masculino , Contracción Muscular/efectos de los fármacos , Ratas
5.
Eur J Clin Pharmacol ; 8(1): 75-8, 1975.
Artículo en Inglés | MEDLINE | ID: mdl-1233204

RESUMEN

The influence of tolbutamide administration on the plasma concentrations of diphenylhydantoin (DPH) was investigated in seventeen long-stay patients with epilepsy. Tolbutamide, 0.5 g 2-3x daily, considerably increased the proportion of non-protein-bound DPH in plasma (mean: 44.6% of control values). The increase was transient, unlike the decrease found in total plasma DPH-concentration (approx. 10% of control values). In vitro experiments confirmed that the interaction between DPH and tolbutamide was due to displacement of DPH from plasma proteins. Some factors that limit the capacity to metabolise DPH in the liver are discussed; they may increase the risk of DPH-intoxication in patients who take sulphonyl-ureas.


Asunto(s)
Fenitoína/sangre , Tolbutamida/farmacología , Adulto , Animales , Proteínas Sanguíneas/metabolismo , Interacciones Farmacológicas , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Fenitoína/uso terapéutico , Unión Proteica/efectos de los fármacos , Ratas
6.
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