The coformulated lopinavir/ritonavir significantly reduces quinine concentration in healthy volunteers due to potential drug-drug interactions (DDIs). However, DDI information in malaria and HIV coinfected patients are lacking. The objective of the study was to apply physiologically-based pharmacokinetic (PBPK) modeling to predict optimal dosage regimens of quinine when coadministered with lopinavir/ritonavir in malaria and HIV coinfected patients with different conditions. The developed model was validated against literature. Model verification was evaluated using the accepted method. The verified PBPK models successfully predicted unbound quinine disposition when coadministered with lopinavir/ritonavir in coinfected patients with different conditions. Suitable dose adjustments to counteract with the DDIs have identified in patients with various situations (i.e., a 7-day course at 1,800 mg t.i.d. in patients with malaria with HIV infection, 648 mg b.i.d. in chronic renal failure, 648 mg t.i.d. in hepatic insufficiency except for severe hepatic insufficiency (324 mg b.i.d.), and 648 mg t.i.d. in CYP3A4 polymorphism).

中文翻译：

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基于生理学的药代动力学模型与奎托宁与利托那韦促进洛匹那韦共同给药的最佳剂量预测。

由于潜在的药物-药物相互作用（DDI），共同配制的lopinavir / ritonavir可显着降低健康志愿者的奎宁浓度。但是，缺乏疟疾和艾滋病毒合并感染患者的DDI信息。这项研究的目的是应用基于生理学的药代动力学（PBPK）模型来预测在与疟疾和HIV合并感染的不同病情患者中，与lopinavir / ritonavir并用时奎宁的最佳剂量方案。所开发的模型已针对文献进行了验证。使用公认的方法评估模型验证。验证的PBPK模型与lopinavir / ritonavir并存于不同病情的合并感染患者中，成功地预测了未结合的奎宁处置。