ArticleBritish journal of clinical pharmacology2017
Characterization of human cytochrome P450 mediated bioactivation of amodiaquine and its major metabolite N-desethylamodiaquine.
Article in British journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- Population pharmacokinetics of artemether-lumefantrine plus amodiaquine in patients with uncomplicated Plasmodium falciparum malaria.British journal of clinical pharmacology · 2026Trial
- Unanticipated CNS Safety Signal in a Placebo-Controlled, Randomized Trial of Co-Administered Atovaquone-Proguanil and Amodiaquine.Clinical pharmacology and therapeutics · 2022Trial
- Humanization of Drug Metabolism in theACS infectious diseases · 2025Article
- In Vitro Metabolism of Doping Agents (Stanozolol, LGD-4033, Anastrozole, GW1516, Trimetazidine) by Human Seminal Vesicle and Liver Fractions.Metabolites · 2025Article
- Precision medication based on the evaluation of drug metabolizing enzyme and transporter functions.Precision clinical medicine · 2025Review
- Effect of Myricetin on CYP2C8 Inhibition to Assess the Likelihood of Drug Interaction UsingACS omega · 2022Article
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- In silico and in vitro screening of licensed antimalarial drugs for repurposing as inhibitors of hepatitis E virus.In silico pharmacology · 2021Article
- Virtual andACS pharmacology & translational science · 2020Article
- Apoptosis contributes to the cytotoxicity induced by amodiaquine and its major metabolite N-desethylamodiaquine in hepatic cells.Toxicology in vitro : an international journal published in association with BIBRA · 2020Article
- Reduction and Scavenging of Chemically Reactive Drug Metabolites by NAD(P)H:Quinone Oxidoreductase 1 and NRH:Quinone Oxidoreductase 2 and Variability in Hepatic Concentrations.Chemical research in toxicology · 2018Article
- GlutathioneFrontiers in pharmacology · 2018Article
- Characterization of human cytochrome P450 mediated bioactivation of amodiaquine and its major metabolite N-desethylamodiaquine.British journal of clinical pharmacology · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsOxidative bioactivation of amodiaquine (AQ) by cytochrome P450s to a reactive quinoneimine is considered as an important mechanism underlying its idiosyncratic hepatotoxicity. However, because internal exposure to its major metabolite N-desethylamodiaquine (DEAQ) is up to 240-fold higher than AQ, bioactivation of DEAQ might significantly contribute to covalent binding. The aim of the present study was to compare the kinetics of bioactivation of AQ and DEAQ by human liver microsomes (HLM) and to characterize the CYPs involved in bioactivation of AQ and DEAQ.
methodsGlutathione was used to trap reactive metabolites formed in incubations of AQ and DEAQ with HLM and recombinant human cytochrome P450s (hCYPs). Kinetics of bioactivation of AQ and DEAQ in HLM and involvement of hCYPs were characterized by measuring corresponding glutathione conjugates (AQ-SG and DEAQ-SG) using a high-performance liquid chromatography method.
resultsBioactivation of AQ and DEAQ in HLM both exhibited Michaelis-Menten kinetics. For AQ bioactivation, enzyme kinetical parameters were K
conclusionsThe major metabolite DEAQ is likely to be quantitatively more important than AQ with respect to hepatic exposure to reactive metabolites in vivo. High expression of CYP3A4, CYP2C8, CYP2C9, and CYP2D6 may be risk factors for hepatotoxicity caused by AQ-therapy.
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