Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Clin Pharmacol Ther. 2012 May;91(5):889-95. doi: 10.1038/clpt.2011.326.
The centuries-old antimalarial drug, quinine, continues to play a critical role in the treatment of severe falciparum malaria and uncomplicated malaria in pregnant women. It shares cytochrome P450 (CYP )-mediated metabolic pathways with several commonly used antiretroviral drugs, raising the potential for clinically important drug–drug interactions. A phase I pharmacokinetic study was conducted to assess the impact of long-term use of ritonavir-boosted lopinavir (LPV/r) on quinine pharmacokinetics in healthy volunteers. LP V/r significantly decreased the exposure of quinine and its major active metabolite, 3-hydroxyquinine, in both total and free (unbound) forms. These findings highlight the complex nature of the influence exerted by LPV/r on several of the drug-metabolizing enzymes involved in quinine disposition,including CYP 3A4, UDP-glucuronosyltransferase (UG T), and P-glycoprotein (P-gp). A decline in quinine exposure may compromise clinical efficacy. Further studies are warranted to assess changes in quinine pharmacokinetics and treatment outcomes in patients with acute malaria receiving antiretroviral therapy that includes LPV/r.
千百年来，奎宁这种抗疟药物在治疗严重的恶性疟原虫疟疾和孕妇的单纯性疟疾方面继续发挥着关键作用。它与几种常用的抗逆转录病毒药物共享细胞色素 P450（CYP）介导的代谢途径，这增加了发生临床重要药物相互作用的潜力。进行了一项 I 期药代动力学研究，以评估长期使用利托那韦增效洛匹那韦（LPV/r）对健康志愿者体内奎宁药代动力学的影响。LPV/r 显著降低了奎宁及其主要活性代谢物 3-羟基奎宁在总形式和游离（未结合）形式下的暴露。这些发现突出了 LPV/r 对涉及奎宁处置的几种药物代谢酶（包括 CYP3A4、UDP-葡萄糖醛酸转移酶（UGT）和 P-糖蛋白（P-gp））产生影响的复杂性。奎宁暴露量的下降可能会影响临床疗效。需要进一步的研究来评估接受包括 LPV/r 在内的抗逆转录病毒治疗的急性疟疾患者的奎宁药代动力学和治疗结果的变化。
