Trenholme G M, Williams R L, Rieckmann K H, Frischer H, Carson P E
Clin Pharmacol Ther. 1976 Apr;19(4):459-67. doi: 10.1002/cpt1976194459.
Quinine disposition was studied in 5 subjects before and during an experimentally induced infection with a chloroquine-resistant strain of Plasmodium falciparum and in 2 individuals before and during artificially induced fever. Plasma quinine levels were determined by both a benzene extraction method (QB), which measures principally unmetabolized quinine, and a metaphosphoric acid precipitation method (QMPA), which measures quinine and quinine metabolites. The ratio QB/QMPA in plasma was used to estimate the extent of metabolism of quinine. In all individuals plasma levels of quinien and QB/QMPA ratios were increased during malaria, suggesting impaired hepatic metabolism of quinine. The changes observed during malaria were not due to altered renal excretion of quinine. In 2 subjects in whom fever was artificially induced there were similar changes in quinine metabolism. These observations suggest that quinine dosage should be modified during the initial period of treatment, when symptoms and fever are greatest, in acute falciparum malaria.
在5名受试者感染实验诱导的抗氯喹恶性疟原虫期间及之前，以及在2名个体人工诱导发热期间及之前，研究了奎宁的处置情况。血浆奎宁水平通过两种方法测定：一种是苯萃取法（QB），主要测量未代谢的奎宁；另一种是偏磷酸沉淀法（QMPA），测量奎宁及其代谢产物。血浆中QB/QMPA的比值用于估计奎宁的代谢程度。在所有个体中，疟疾期间血浆奎宁水平和QB/QMPA比值均升高，提示奎宁的肝脏代谢受损。疟疾期间观察到的变化并非由于奎宁肾排泄改变所致。在2名人工诱导发热的受试者中，奎宁代谢也有类似变化。这些观察结果表明，在急性恶性疟治疗的初期，即症状和发热最严重时，应调整奎宁剂量。
