[Microsomal oxidative metabolism in the liver of rats treated with vinorelbine: evaluation through antipyrine elimination].
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.
Servicio de Farmacia, Hospital Militar Central Gómez-Ulla, Madrid, Spain. pimontenegro@terra.es
P
P
Montenegro-Alvarez
M
M
González-Alfonso
M H
MH
Cantarino-Aragón
C
C
Gutiérrez-Ortega
F J
FJ
Guijarro-Escribano
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000983:Antipyrine / Q000493:pharmacokinetics*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D000077235:Vinorelbine; D000983:Antipyrine