Trial reportAntimicrobial agents and chemotherapy2010
Influence of alpha-1 glycoprotein acid concentrations and variants on atazanavir pharmacokinetics in HIV-infected patients included in the ANRS 107 trial.
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 11 papers.
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.
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Who cites it
11 citing papers in PubMed, 29 citations in OpenAlex.
- Sex differences in atazanavir pharmacokinetics and associations with time to clinical events: AIDS Clinical Trials Group Study A5202.The Journal of antimicrobial chemotherapy · 2014Trial
- Effect of protein binding on unbound atazanavir and darunavir cerebrospinal fluid concentrations.Journal of clinical pharmacology · 2014Trial
- Population pharmacokinetic modeling of the association between 63396C->T pregnane X receptor polymorphism and unboosted atazanavir clearance.Antimicrobial agents and chemotherapy · 2010Trial
- Integrating in vitro data and physiologically based kinetic modeling-facilitated reverse dosimetry to predict human cardiotoxicity of methadone.Archives of toxicology · 2020Article
- Effect of Plasma Protein Binding on the Anti-Hepatitis B Virus Activity and Pharmacokinetic Properties of NVR 3-778.Antimicrobial agents and chemotherapy · 2018Article
- Preclinical pharmacokinetics and tissue distribution of long-acting nanoformulated antiretroviral therapy.Antimicrobial agents and chemotherapy · 2013Article
- Clinical pharmacokinetics of antiretroviral drugs in older persons.Expert opinion on drug metabolism & toxicology · 2013Review
- Implications of plasma protein binding for pharmacokinetics and pharmacodynamics of the γ-secretase inhibitor RO4929097.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Article
- Pharmacokinetics and Pharmacodynamics of Darunavir and Etravirine in HIV-1-Infected, Treatment-Experienced Patients in the Gender, Race, and Clinical Experience (GRACE) Trial.AIDS research and treatment · 2012Article
- Calculation of normalized drug concentrations in the presence of altered plasma protein binding.Clinical pharmacokinetics · 2012Article
- Atazanavir/ritonavir-based combination antiretroviral therapy for treatment of HIV-1 infection in adults.Future virology · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Atazanavir is an HIV-1 protease inhibitor with high protein binding in human plasma. The objectives were first to determine the in vitro binding characteristics of atazanavir and second to evaluate whether plasma protein binding to albumin and alpha-1 glycoprotein acid (AAG) influences the pharmacokinetics of atazanavir in HIV-infected patients. For the in vitro study, atazanavir protein binding characteristics were determined in AAG- and albumin-containing purified solutions. Atazanavir was found to bind AAG on a high-affinity saturable site (association constant, 4.61x10(5) liters/mol) and albumin on a low-affinity nonsaturable site. For the in vivo study, blood samples from 51 patients included in trial ANRS 107--Puzzle 2 were drawn prior to drug intake at week 6. For 10 patients included in the pharmacokinetic substudy, five additional blood samples were collected during one dosing interval at week 6. Atazanavir concentrations were assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Albumin concentrations, AAG concentrations, and phenotypes were also measured in these patients. Concentrations of atazanavir were modeled using a population approach. A one-compartment model with first-order absorption and elimination best described atazanavir pharmacokinetics. Atazanavir pharmacokinetic parameters and their interindividual variabilities were as follows: absorption rate constant (ka), 0.73 h(-1) (139.3%); apparent clearance (CL/F), 13.3 liters/h (26.7%); and apparent volume of distribution (V/F), 79.7 liters (27.0%). Atazanavir CL/F decreased significantly when alanine aminotransferase and/or AAG levels increased (P<0.01). The ORM1*S phenotype also significantly increased atazanavir V/F (P<0.05). These in vivo results indicate that atazanavir pharmacokinetics is moderately influenced by its protein binding, especially to AAG, without expected clinical consequences.
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