RESUMO
The pharmacokinetics of vinblastine in humans was examined using a radioimmunoassay specific for both the Vinca alkaloids and aromatic ring [3H]vinblastine. The data were consistent with a three-compartment open model system with the following values, alpha phase: t1/2=3.90+/-1.46 min; Vc=16.8+/-7.1 liters. beta phase:t1/2=53.0+/-13.0 min; Vbeta=79.0+/-52.0 liters; gamma phase:t1/2=1173.0+/-65.0 min; Vgamma=1656.0+/-717.0 liters. Most significant was the finding that vinblastine is metabolized to deacetylvinblastine and that this compound is more biologically active on a weight basis than the parent. No other biologically active metabolites appeared to be present in urine or in stool.
Assuntos
Vimblastina/metabolismo , Fezes/análise , Humanos , Cinética , Radioimunoensaio , Vimblastina/sangue , Vimblastina/urinaRESUMO
Vindesine, a new Phase 1 Vinca alkaloid congener, exhibited serum pharmacokinetic behavior in humans compatible with a three-compartment, open mammilary model. The kinetic parameters included: t1/2 alpha=3.24+/-1.14 min, t1/2beta=99.0+/-44.5 min, t1/2gamma=1213+/-493 min, Vc (Valpha)=4.81+/-2.12 liters, Vbeta=58.2+/-50.5 liters, Vgamma=598+/-294 liters. Vincristine, studied only for the first 4 hr, behaved like a two-compartment system, with values of t1/2 alpha=3.37+/-0.72 min, t1/2beta=155+/-18 min, Valpha=4.53+/-0.49 liters, and Vbeta=57.3+/-21.1 liters. Urine excretion data demonstrated that most drug elimination occurred within the first 24 hr and amounted to 13.2+/-5.9% for vindesine and 9.5+/-5.1% for vincristine.
Assuntos
Vimblastina/análogos & derivados , Vincristina/sangue , Humanos , Cinética , Taxa de Depuração Metabólica , Radioimunoensaio , Vimblastina/sangue , Alcaloides de Vinca/metabolismo , Alcaloides de Vinca/urina , Vincristina/metabolismo , Vincristina/urinaAssuntos
Alcaloides de Vinca/farmacologia , Animais , Antineoplásicos/uso terapêutico , Sítios de Ligação/efeitos dos fármacos , Ligação Competitiva/efeitos dos fármacos , Feminino , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Cinética , Dose Letal Mediana , Leucemia Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos , Ligação Proteica/efeitos dos fármacos , Solubilidade , Suínos , Tubulina (Proteína)/metabolismo , Alcaloides de Vinca/metabolismo , Alcaloides de Vinca/toxicidadeRESUMO
A series of Vinca alkaloids were found to block polymerization of crude tubulin extracts of porcine brain in a dose-dependent manner. This appears to be a specific effect occurring at low concentrations of drug. The concentration of vinblastine that prevents polymerization by 50% was 4.3 x 10(-7) mole/liter for a tubulin concentration of 3.0 mg/ml, and this concentration is consistent with levels achieved in vivo following routine pharmacological doses in humans.
