ReviewEuropean journal of clinical pharmacology2014
Impact of CYP polymorphisms, ethnicity and sex differences in metabolism on dosing strategies: the case of efavirenz.
Review in European journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
What it found
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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
27 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Interactions of Antiretroviral Drugs with Food, Beverages, Dietary Supplements, and Alcohol: A Systematic Review and Meta-analyses.AIDS and behavior · 2023Pooled it
- Inter-ethnic differences in pharmacokinetics-is there more that unites than divides?Pharmacology research & perspectives · 2021Pooled it
- High efavirenz levels but not neurofilament light plasma levels are associated with poor neurocognitive functioning in asymptomatic HIV patients.Journal of neurovirology · 2020Trial
- Methadone Pharmacogenetics: CYP2B6 Polymorphisms Determine Plasma Concentrations, Clearance, and Metabolism.Anesthesiology · 2015Trial
- Impact of Dihydrocapsaicin on the Metabolism of Efavirenz In Vitro and In Vivo.Pharmacology research & perspectives · 2025Article
- Article
- Sub- and supratherapeutic efavirenz plasma concentrations with risk for HIV therapy failure are mainly genetically explained in Ugandan children: The prospective GENEFA cohort study.British journal of clinical pharmacology · 2025Article
- PBPK Modeling of Lamotrigine and Efavirenz during Pregnancy: Implications for Personalized Dosing and Drug-Drug Interaction Management.Pharmaceutics · 2024Article
- Review
- Protein Abundance of Drug Metabolizing Enzymes in Human Hepatitis C Livers.International journal of molecular sciences · 2023Article
- Joint Analysis of Phenotypic and Genomic Diversity Sheds Light on the Evolution of Xenobiotic Metabolism in Humans.Genome biology and evolution · 2022Article
- Normal variation of the gut microbiota affects hepatic cytochrome P450 activity in mice.Pharmacology research & perspectives · 2021Article
- Inter-individual and inter-regional variations in enteric drug metabolizing enzyme activities: Results with cryopreserved human intestinal mucosal epithelia (CHIM) from the small intestines of 14 donors.Pharmacology research & perspectives · 2020Article
- Prediction of the exposure to a 400-mg daily dose of efavirenz in pregnancy: is this dose adequate in extensive metabolisers of CYP2B6?European journal of clinical pharmacology · 2020Article
- Effect of efavirenz on levonorgestrel concentrations among Malawian levonorgestrel implant users for up to 30 months of concomitant use: a subanalysis of a randomized clinical trial.Contraception: X · 2020Article
- Role of efavirenz plasma concentrations on long-term HIV suppression and immune restoration in HIV-infected children.PloS one · 2019Observational
- Neuropsychiatric and Neurocognitive Manifestations in HIV-Infected Children Treated With Efavirenz in South Africa-A Retrospective Case Series.Frontiers in neurology · 2019Article
- Priming the body to receive the therapeutic agent to redefine treatment benefit/risk profile.Scientific reports · 2018Article
- HIV and mental illness in Malawi and the neuropsychiatric sequelae of efavirenz.Malawi medical journal : the journal of Medical Association of Malawi · 2018Review
- Efavirenz Therapeutic Range in HIV-1 Treatment-Naive Participants.Therapeutic drug monitoring · 2017Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeDifferences in drug metabolism due to cytochrome P450 (CYP) polymorphisms may be significant enough to warrant different dosing strategies in carriers of specific cytochrome P450 (CYP) polymorphisms, especially for drugs with a narrow therapeutic index. The impact of such polymorphisms on drug plasma concentrations and the resulting dosing strategies are presented in this review, using the example of efavirenz (EFV).
methodsA structured literature search was performed to extract information pertaining to EFV metabolism and the influence of polymorphisms of CYP2B6, ethnicity, sex and drug interactions on plasma concentrations of EFV. The corresponding dosing strategies developed for carriers of specific CYP2B6 genotypes were also reviewed.
resultsThe polymorphic CYP2B6 enzyme, which is the major enzyme in the EFV metabolic pathway, is a key determinant for the significant inter-individual differences seen in EFV pharmacokinetics and pharmacodynamics (PKPD). Ethnic differences and the associated prevalence of CYP2B6 polymorphisms result in significant differences in the PKPD associated with a standard 600 mg per day dose of EFV, warranting dosage reduction in carriers of specific CYP2B6 polymorphisms. Drug interactions and auto-induction also influence EFV PKPD significantly.
conclusionUsing EFV as an example of a drug with a narrow therapeutic index and a high inter-patient variability in plasma concentrations corresponding to a standard dose of the drug, this review demonstrates how genotyping of the primary metabolising enzyme can be useful for appropriate dosage adjustments in individuals. However, other variables such as drug interactions and auto-induction may necessitate plasma concentration measurements as well, prior to personalising the dose.
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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.