Trial reportAntimicrobial agents and chemotherapy2010
Population pharmacokinetic modeling of the association between 63396C->T pregnane X receptor polymorphism and unboosted atazanavir clearance.
Trial report in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis 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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Genetic variation on dolutegravir pharmacokinetics and relation to safety and efficacy outcomes: a systematic review.Pharmacogenomics · 2024Pooled it
- Influence of body weight and UGT2B7 polymorphism on varenicline exposure in a cohort of smokers from the general population.European journal of clinical pharmacology · 2019Trial
- Pharmacogenetic Analysis of the Model-Based Pharmacokinetics of Five Anti-HIV Drugs: How Does This Influence the Effect of Aging?Clinical and translational science · 2018Trial
- Effect of Single Nucleotide Polymorphisms in the Xenobiotic-sensing Receptors NR1I2 and NR1I3 on the Pharmacokinetics and Toxicity of Irinotecan in Colorectal Cancer Patients.Clinical pharmacokinetics · 2016Trial
- Comprehensive Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Evaluation of Once-Daily Efavirenz 400 and 600 mg in Treatment-Naïve HIV-Infected Patients at 96 Weeks: Results of the ENCORE1 Study.Clinical pharmacokinetics · 2016Trial
- Role of the lean body mass and of pharmacogenetic variants on the pharmacokinetics and pharmacodynamics of sunitinib in cancer patients.Investigational new drugs · 2015Trial
- Genomewide association study of atazanavir pharmacokinetics and hyperbilirubinemia in AIDS Clinical Trials Group protocol A5202.Pharmacogenetics and genomics · 2014Trial
- Pharmacogenetic effects of regulatory nuclear receptors (PXR, CAR, RXRα and HNF4α) on docetaxel disposition in Chinese nasopharyngeal cancer patients.European journal of clinical pharmacology · 2014Trial
- Simultaneous pharmacogenetics-based population pharmacokinetic analysis of darunavir and ritonavir in HIV-infected patients.Clinical pharmacokinetics · 2013Trial
- Investigating PXR (NR1I2) genetic polymorphisms as possible determinants of the magnitude of the clindamycin-rifampicin pharmacokinetic interaction.European journal of clinical pharmacology · 2026Article
- Pharmacogenomics of antibacterial and antiviral therapies: Clinical actionability, evidence gaps, and future directions.Pharmacological reviews · 2026Review
- Association of NR1I2 Polymorphism with Midazolam Clearance in Mechanically Ventilated ICU Patients: A Population Pharmacokinetic and Pharmacogenetic Study.Drug design, development and therapy · 2025Article
- Pregnane X Receptor (PXR) Polymorphisms and Cancer Treatment.Biomolecules · 2021Review
- Review
- Association of Pharmacogenetic Markers With Atazanavir Exposure in HIV-Infected Women.Clinical pharmacology and therapeutics · 2020Observational
- A Genome-Wide Association Study Identifies a Candidate Gene Associated With Atazanavir Exposure Measured in Hair.Clinical pharmacology and therapeutics · 2018Observational
- Pharmacokinetic Changes during Pregnancy According to Genetic Variants: a Prospective Study in HIV-Infected Patients Receiving Atazanavir-Ritonavir.Antimicrobial agents and chemotherapy · 2018Article
- PharmGKB summary: atazanavir pathway, pharmacokinetics/pharmacodynamics.Pharmacogenetics and genomics · 2018Article
- The Role of PXR Genotype and Transporter Expression in the Placental Transport of Lopinavir in Mice.Pharmaceutics · 2017Article
- The Effect of Gene Variants on Levonorgestrel Pharmacokinetics When Combined With Antiretroviral Therapy Containing Efavirenz or Nevirapine.Clinical pharmacology and therapeutics · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 7 institutions in 4 countries.
Funding
Abstract
Atazanavir (ATV) plasma concentrations are influenced by CYP3A4 and ABCB1, which are regulated by the pregnane X receptor (PXR; NR1I2). PXR expression is correlated with CYP3A4 in liver in the absence of enzyme inducers. The PXR single nucleotide polymorphism (SNP) 63396C→T (rs2472677) alters PXR expression and CYP3A4 activity in vitro, and we previously showed an association of this polymorphism with unboosted ATV plasma concentrations. The aim of this study was to develop a population pharmacokinetic analysis to quantify the impact of 63396C→T and diurnal variation on ATV clearance. A population analysis was performed with 323 plasma samples from 182 randomly selected patients receiving unboosted ATV. Two hundred fifty-nine of the blood samples were collected at random time points, and 11 patients had a full concentration-time profile at steady state. Nonlinear mixed effects modeling was applied to explore the effects of PXR 63396C→T, patient demographics, and diurnal variation. A one-compartment model with first-order absorption and lag time best described the data. Population clearance was 19.7 liters/h with interpatient variability or coefficient of variation (CV) of 21.5%. Homozygosity for the T allele for PXR 63396 was associated with a 17.0% higher clearance that was statistically significant. Evening dosing was associated with 34% higher bioavailability than morning dosing. Patient demographic factors had no effect on ATV clearance. These data show an association of PXR 63396C→T and diurnal variation on unboosted ATV clearance. The association is likely to be mediated through an effect on hepatic PXR expression and therefore expression of its target genes (e.g., CYP3A4, SLCO1B1, and ABCB1), which are known to be involved in ATV clearance.
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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.