Physiologically-Based Pharmacokinetic Modeling for Optimal Dosage Prediction of Quinine Coadministered With Ritonavir-Boosted Lopinavir



Saeheng, Teerachat, Na-Bangchang, Kesara, Siccardi, Marco ORCID: 0000-0002-3539-7867, Rajoli, Rajith KR ORCID: 0000-0002-6015-5712 and Karbwang, Juntra
(2020) Physiologically-Based Pharmacokinetic Modeling for Optimal Dosage Prediction of Quinine Coadministered With Ritonavir-Boosted Lopinavir. CLINICAL PHARMACOLOGY & THERAPEUTICS, 107 (5). pp. 1209-1220.

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Abstract

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).

Item Type: Article
Uncontrolled Keywords: Humans, HIV Infections, Malaria, Quinine, Ritonavir, Drug Combinations, HIV Protease Inhibitors, Antimalarials, Dose-Response Relationship, Drug, Drug Interactions, Models, Biological, Adolescent, Adult, Middle Aged, Young Adult, Lopinavir, Coinfection
Depositing User: Symplectic Admin
Date Deposited: 06 Dec 2019 12:43
Last Modified: 19 Jan 2023 00:13
DOI: 10.1002/cpt.1721
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3065181