In vitro hepatic metabolism of cinchona antimalarials by hamster enzymes

Cinchona alkaloids [quinidine and cinchonine] were incubated with aldehyde oxidase and microsomal monooxygenases from hamster liver. Reversed-phase HPLC method was used to separate quinidine and cichonine from their metabolites. Characterisation of the metabolites arising from aldehyde oxidase by infrared and mass spectral analysis, exhibited that quinidine and cinchonine were oxidised to the corresponding 2'-quinolones. In vitro microsomal metabolites of quinidine were identified as 2'-quinidinone and O-desmethylquinidine. Incubation of cinchonine with microsomal enzymes showed that no metabolites were generated

Monitorizaçäo das concentraçöes plasmáticas de quinina em pacientes com malária por P. Falciparum / Monitorization of the plasmatic concentrations of quinine in patients with malaria per P. Falciparum

A quinina é o quimioterápico de escolha no tratamento da malária falciparum resistente à cloroquina, importante patologia cuja incidência aumenta anualmente. Considerando-se o conjunto dos efeitos tóxicos da quinina (cinchonismo), as variaçöes na sua cinética durante episódios de malária näo grave e os esquemas terapêuticos divergentes adotados no país, este estudo tem como objetivo determinar as concentraçöes plasmáticas da quinina em amostras de plasma de pacientes com malária falciparum na forma näo grave com as finalidades de: minimizar o cinchonismo e reduzir as possibilidades de resistência do P. falciparum ao quimioterápico. Os resultados demonstraram que o procedimento analítico proposto e validado para a determinaçäo dos níveis plasmáticos de quinina apresentou valores que indicam sua aplicabilidade na monitorizaçäo terapêutica. A determinaçäo de quinina nos pacientes apresentou valores, a partir do segundo dia de tratamento, de 2,33 a 16,89 µg/mL, indicando a eficácia do esquema terapêutico empregado. Foram detectados, nas avaliaçöes clínicas, sinais e sintomas associados ao cinchonismo. Os pacientes näo apresentaram episódios de hipoglicemia. O esquema terapêutico empregado apresentou eficácia de 100 por cento sobre as formas assexuadas de P. falciparum, indicando a inexistência de resistência ao quimioterápico...

Pharmacokinetics of quinine, quinidine and Cinchonine when given as combination.

Pharmacokinetics of quinine, quinidine and cinchonine when given as a combination were evaluated in Thai patients with falciparum malaria during acute infection and convalescence. The combination of quinine, quinidine and cinchonine was randomly given to thirteen patients at 400 mg or 600 mg (consisting of one-third of each component; 7 patients were enrolled in 400 mg regimen and 6 in 600 mg regimen) intravenously every 8 hours for 7 days. The drug combination was given again at day 35 to define the pharmacokinetics of each drug during convalescence. All patients with the 600 mg regimen had good response with 100% cure rate while patients with the 400 mg regimen had a good initial response but one patient recrudesed on day 46. This particular patient had plasma concentrations of all three drugs lower than the mean values of patients with sensitive responses. The plasma levels of quinine and quinidine obtained from the present study were higher than that expected from one-third of the conventional dose (600 mg) when given alone, suggesting drug combination interaction. The terminal half-lives of each of the three components were prolonged during acute malaria when compared to those obtained during convalescence.