[Microsomal oxidative metabolism in the liver of rats treated with vinorelbine: evaluation through antipyrine elimination]. / Evaluación del metabolismo oxidativo microsómico hepático en ratas tratadas con vinorelbina mediante la eliminación de antipirina.

BACKGROUND: Determination of the metabolic efficiency of the liver in neoplastic diseases in patients receiving highly toxic drugs is of great practical importance. METHODS: The effect of vinorelbine on the metabolic efficiency of the liver was evaluated by means of phenazone kinetics in rats. The test was compared with a battery of tests routinely used whenever hepatic dysfunction is suspected. RESULTS: Vinorelbine was administered to the rats and the pharmacokinetic parameters of antipyrine were compared with those in control rats. A statistically significant prolongation of the elimination half-life, as well as a decrease in the elimination constant and clearance of antipyrine were found in the rats receiving the anticancer drug in comparison with controls (p < 0.01). Statistically significant correlations were found between the elimination half-life of antipyrine and serum albumin values (p < 0.01) and prothrombin time (p < 0.001). CONCLUSIONS: Determination of antipyrine pharmacokinetics allows early detection of vinorelbine-induced hepatic dysfunction, with a sensitive scale.

Evaluación del metabolismo oxidativo microsómico hepático en ratas tratadas con vinorelbina mediante la eliminación de antipirina / Microsomal oxidative metabolism in the liver of rats treated with vinorelbine: evaluation through antipyrine elimination

Introducción: Conocer la eficacia metabólica del hígado de pacientes en tratamiento con fármacos altamente tóxicos es de gran importancia clínica. Material y métodos: En el presente trabajo se ha evaluado el efecto, en ratas, de la administración de vinorelbina sobre la eficacia metabólica del hígado mediante los parámetros farmacocinéticos de la fenazona. Asimismo se han comparado con pruebas habitualmente utilizadas cuando se sospecha una disfunción hepática. Resultados: Tras la administración de vinorelbina en ratas los parámetros farmacocinéticos de antipirina cambiaron significativamente al compararlos con los de ratas control. En las tratadas con vinorelbina se produjo una prolongación de la vida media de la antipirina, así como una disminución de la constante de eliminación y del aclaramiento, cambios que fueron estadísticamente significativos (p < 0,01). Al mismo tiempo, se hallaron relaciones estadísticamente significativas entre la vida media de la antipirina y las concentraciones de albúmina sérica (p < 0,01), al igual que con el tiempo de protrombina (p < 0,001). Conclusión: La prueba de antipirina permite la detección temprana de disfunción oxidativa, producida por vinorelbina, con una escala sensitiva

Background: Determination of the metabolic efficiency of the liver in neoplastic diseases in patients receiving highly toxic drugs is of great practical importance. Methods: The effect of vinorelbine on the metabolic efficiency of the liver was evaluated by means of phenazone kinetics in rats. The test was compared with a battery of tests routinely used whenever hepatic dysfunction is suspected. Results: Vinorelbine was administered to the rats and the pharmacokinetic parameters of antipyrine were compared with those in control rats. A statistically significant prolongation of the elimination half-life, as well as a decrease in the elimination constant and clearance of antipyrine were found in the rats receiving the anticancer drug in comparison with controls (p < 0.01). Statistically significant correlations were found between the elimination half-life of antipyrine and serum albumin values (p < 0.01) and prothrombin time (p < 0.001). Conclusions: Determination of antipyrine pharmacokinetics allows early detection of vinorelbine-induced hepatic dysfunction, with a sensitive scale