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Selecting an anti-malarial clinical candidate from two potent dihydroisoquinolones

February 23, 2021 - 14:17 -- Open Access
Yizhe Chen, Fangyi Zhu, R. Kiplin Guy, et al.
Malaria Journal 2021 20:107, 19 February 2021

The ongoing global malaria eradication campaign requires development of potent, safe, and cost-effective drugs lacking cross-resistance with existing chemotherapies. One critical step in drug development is selecting a suitable clinical candidate from late leads. The process used to select the clinical candidate SJ733 from two potent dihydroisoquinolone (DHIQ) late leads, SJ733 and SJ311, based on their physicochemical, pharmacokinetic (PK), and toxicity profiles is described.

Drug-drug Interactions between Lumefantrine and Commonly-used Antiretroviral Treatment: An Individual Participant Data Population Pharmacokinetic Meta-Analysis

February 24, 2020 - 14:10 -- Open Access
Francis J, Barnes KI, Denti P, et al.
Antimicrob Agents Chemother. 2020 Feb 18. pii: AAC.02394-19

Treating malaria in HIV co-infected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly-used antiretrovirals often induce or inhibit. A population pharmacokinetic meta-analysis was conducted using individual participant data from ten studies, with 6,100 lumefantrine concentrations from 793 non-pregnant adult participants (41% HIV-malaria co-infected, 36% malaria-infected, 20% HIV-infected, and 3% healthy volunteers).

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