ArticleEuropean journal of clinical pharmacology2012
Metabolism of alprazolam (a marker of CYP3A4) in hemodialysis patients with persistent inflammation.
Article in European journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 27 citations in OpenAlex.
- Inflammation down-regulates CYP3A4-catalysed drug metabolism in hemodialysis patients.BMC pharmacology & toxicology · 2018Trial
- Applications of the Cholesterol Metabolite, 4β-Hydroxycholesterol, as a Sensitive Endogenous Biomarker for Hepatic CYP3A Activity Evaluated within a PBPK Framework.Pharmaceutics · 2024Article
- Single-Cell RNA-Sequencing Analysis of Colonic Lamina Propria Immune Cells Reveals the Key Immune Cell-Related Genes of Ulcerative Colitis.Journal of inflammation research · 2023Article
- Changes in Alprazolam Metabolism by CYP3A43 Mutants.Biomedicines · 2022Article
- The Role of CYP3A in Health and Disease.Biomedicines · 2022Review
- Body composition is associated with tacrolimus pharmacokinetics in kidney transplant recipients.European journal of clinical pharmacology · 2022Article
- The role of cytochromes P450 in the metabolism of selected antidepressants and anxiolytics under psychological stress.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2022Review
- Impact of Acute Inflammation on Cytochromes P450 Activity Assessed by the Geneva Cocktail.Clinical pharmacology and therapeutics · 2021Observational
- Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature.Frontiers in pharmacology · 2021Review
- Significant increase in plasma 4β-hydroxycholesterol concentration in patients after kidney transplantation.Journal of lipid research · 2013Article
- Pharmacokinetics, pharmacodynamics and physiologically-based pharmacokinetic modelling of monoclonal antibodies.Clinical pharmacokinetics · 2013Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo investigate the impact of persistent inflammation in hemodialysis (HD) patients on the pharmacokinetics of alprazolam, a cytochrome P450 (CYP) 3A4 substrate, and its metabolites and the role of HD in the impact of persistent inflammation in this clinical context.
methodsThe study population comprised 26 HD patients (mean age 64 years, range 27-79 years; 19 men, 7 women) who were given 1 mg of alprazolam orally in the evening before the day of HD. Unconjugated and conjugated alprazolam and its 4-hydroxy and α-hydroxy metabolites were measured by liquid chromatography-mass spectrometry at 10, 34 (start of HD) and 38 (end of HD) h after intake. C-reactive protein (CRP) was measured weekly beginning 2 months before study initiation, and alpha 1-acid glycoprotein and 4β-hydroxycholesterol were measured at baseline. CYP3A4 activity was estimated as the ratio of unconjugated alprazolam to 4-hydroxyalprazolam between 10 and 34 h following alprazolam intake.
resultsAfter a single dose of alprazolam, plasma concentrations of unconjugated alprazolam and its metabolites decreased gradually, and unconjugated 4-hydroxyalprazolam was eliminated more rapidly than unconjugated alprazolam by HD. In contrast, the plasma concentrations of conjugated alprazolam and its conjugated metabolites increased during the 34 h following drug intake and the subsequent HD decreased their levels by almost 80%. The ratio of unconjugated alprazolam to 4-hydroxyalprazolam was correlated with CRP levels (r(s) = 0.49, P = 0.01). There was no significant correlation between CYP3A4 activity measured by alprazolam (4-hydroxylation) and alpha 1-acid glycoprotein or 4β-hydroxycholesterol. Conjugated alprazolam was also found in the plasma.
conclusionsThe correlation between CYP3A4 activity (assessed by alprazolam 4-hydroxylation) and CRP level suggests that inflammation may downregulate CYP3A4 activity. If confirmed, this could have major implications for drug dosing in persistently inflamed patients.
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