ArticleXenobiotica; the fate of foreign compounds in biological systems2012
In vitro metabolism of piperaquine is primarily mediated by CYP3A4.
Article in Xenobiotica; the fate of foreign compounds in biological systems, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Population pharmacokinetics of amodiaquine and piperaquine in African pregnant women with uncomplicated Plasmodium falciparum infections.CPT: pharmacometrics & systems pharmacology · 2024Trial
- Impact of Dolutegravir-Based Antiretroviral Therapy on Piperaquine Exposure following Dihydroartemisinin-Piperaquine Intermittent Preventive Treatment of Malaria in Pregnant Women Living with HIV.Antimicrobial agents and chemotherapy · 2022Trial
- Trial
- Optimal dosing of dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in young children.Nature communications · 2019Trial
- Pharmacokinetics of Piperaquine and Safety Profile of Dihydroartemisinin-Piperaquine Coadministered with Antiretroviral Therapy in Malaria-Uninfected HIV-Positive Malawian Adults.Antimicrobial agents and chemotherapy · 2018Trial
- Dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria during pregnancy and risk of malaria in early childhood: A randomized controlled trial.PLoS medicine · 2018Trial
- Population pharmacokinetics and electrocardiographic effects of dihydroartemisinin-piperaquine in healthy volunteers.British journal of clinical pharmacology · 2017Trial
- Antiretroviral Therapy With Efavirenz Accentuates Pregnancy-Associated Reduction of Dihydroartemisinin-Piperaquine Exposure During Malaria Chemoprevention.Clinical pharmacology and therapeutics · 2017Trial
- Pharmacokinetic Interactions between Tafenoquine and Dihydroartemisinin-Piperaquine or Artemether-Lumefantrine in Healthy Adult Subjects.Antimicrobial agents and chemotherapy · 2016Trial
- Artemisinin-based combination therapies are efficacious and safe for treatment of uncomplicated malaria in HIV-infected Ugandan children.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2014Trial
- Impact of Dolutegravir-, Lopinavir/Ritonavir-, and Efavirenz-Based Antiretrovirals on Piperaquine Pharmacokinetics in Ugandan Children Living with HIV.Clinical pharmacology and therapeutics · 2026Article
- Physiologically-Based Pharmacokinetic Modeling to Investigate Piperaquine Exposure in Pregnant Women Using an Individualized Profile Approach.Clinical and translational science · 2026Article
- Evaluation of in vitro drug-drug interactions of ivermectin and antimalarial compounds.Malaria journal · 2025Article
- A Comprehensive Review on the Pharmacokinetics and Bioanalysis of Piperaquine.Current drug metabolism · 2025Review
- Pharmacokinetics of piperaquine and its association with intermittent malaria preventive therapy outcomes during pregnancy.BMC pharmacology & toxicology · 2024Article
- Magnitude of Drug-Drug Interactions in Special Populations.Pharmaceutics · 2022Review
- Assessing the Roles of Molecular Markers of Antimalarial Drug Resistance and the Host Pharmacogenetics in Drug-Resistant Malaria.Journal of tropical medicine · 2022Review
- Malaria PK/PD and the Role Pharmacometrics Can Play in the Global Health Arena: Malaria Treatment Regimens for Vulnerable Populations.Clinical pharmacology and therapeutics · 2021Review
- Effect of Dihydroartemisinin-Piperaquine on the Pharmacokinetics of Praziquantel for Treatment ofPharmaceuticals (Basel, Switzerland) · 2021Article
- Piperaquine Exposure Is Altered by Pregnancy, HIV, and Nutritional Status in Ugandan Women.Antimicrobial agents and chemotherapy · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Piperaquine (PQ) is part of a first-line treatment regimen for Plasmodium falciparum malaria recommended by the World Health Organization (WHO). We aimed to determine the major metabolic pathway(s) of PQ in vitro. A reliable, validated tandem mass spectrometry method was developed. Concentrations of PQ were measured after incubation with both human liver microsomes (HLMs) and expressed cytochrome P450 enzymes (P450s). In pooled HLMs, incubations with an initial PQ concentration of 0.3 µM resulted in a 34.8 ± 4.9% loss of substrate over 60 min, corresponding to a turnover rate of 0.009 min(-1) (r(2) = 0.9223). Miconazole, at nonspecific P450 inhibitory concentrations, resulted in almost complete inhibition of PQ metabolism. The greatest inhibition was demonstrated with selective CYP3A4 (100%) and CYP2C8 (66%) inhibitors. Using a mixture of recombinant P450 enzymes, turnover for PQ metabolism was estimated as 0.0099 min(-1); recombinant CYP3A4 had a higher metabolic rate (0.017 min(-1)) than recombinant CYP2C8 (p < .0001). Inhibition of CYP3A4-mediated PQ loss was greatest using the selective inhibitor ketoconazole (9.1 ± 3.5% loss with ketoconazole vs 60.7 ± 5.9% with no inhibitor, p < .0001). In summary, the extent of inhibition of in vitro metabolism with ketoconazole (83%) denotes that PQ appears to be primarily catalyzed by CYP3A4. Further studies to support these findings through the identification and characterization of PQ metabolites are planned.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.