ArticleBritish journal of clinical pharmacology2014
CYP3A activity in severe liver cirrhosis correlates with Child-Pugh and model for end-stage liver disease (MELD) scores.
Article in British 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 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Re-discover the value of protein binding assessments in hepatic and renal impairment studies and its contributions in drug labels and dose decisions.Clinical and translational science · 2024Pooled it
- Pharmacokinetics of Ipatasertib in Subjects With Hepatic Impairment Using 2 Methods of Classification of Hepatic Function.Journal of clinical pharmacology · 2022Trial
- Safety of Chronic Simvastatin Treatment in Patients with Decompensated Cirrhosis: Many Adverse Events but No Liver Injury.Digestive diseases and sciences · 2021Trial
- A real-world multicenter study of statins in compensated advanced chronic liver disease on hepatic decompensation and mortality outcomes.Hepatology international · 2026Article
- Population Pharmacokinetic Analysis of Everolimus Based on Albumin-Bilirubin Scores in Kidney Transplant Recipients.European journal of drug metabolism and pharmacokinetics · 2026Article
- Introducing the TOP framework: a novel phenotyping solution for collaborative phenotype algorithm development and application.Journal of biomedical semantics · 2026Article
- Mutant-Selective Binding ofInternational journal of molecular sciences · 2026Article
- Comprehensive Pathophysiology Repository for PBPK Modeling in Liver Cirrhosis: Quantifying Continuous Disease Progression and Population Variability.CPT: pharmacometrics & systems pharmacology · 2026Article
- TLR4-Mediated Immune Dysfunction Links MASLD and Parkinson's Disease: Insights from an Omics-Based Network Analysis.NeuroSci · 2026Article
- Continuation of sedative infusions during palliative extubation for refractory status epilepticus in hepatic encephalopathy: A case report.SAGE open medical case reports · 2026Article
- Medication safety in patients with hepatic disease: proof of concept of a new approach to screen for patients at risk-a retrospective evaluation utilizing electronic prescribing systems.International journal of clinical pharmacy · 2025Article
- Liver microsomal protein content and activity in patients with hepatocellular carcinoma and cirrhosis: implications for theJournal of gastrointestinal oncology · 2025Article
- Alcohol-related liver disease.Gastroenterology report · 2025Review
- Phenoconversion andHepatology forum · 2025Review
- Article
- Hepatic Impairment as a Risk Factor for Drug Safety: Suitability and Comparison of Four Liver Scores as Screening Tools.Journal of clinical medicine · 2023Article
- Review of the role of statins in cirrhosis and portal hypertension.Clinical liver disease · 2023Article
- Effects of chronic cirrhosis induced by intraperitoneal thioacetamide injection on the protein content and Michaelis-Menten kinetics of cytochrome P450 enzymes in the rat liver microsomes.Basic & clinical pharmacology & toxicology · 2023Article
- JCS/JHRS 2020 Guideline on Pharmacotherapy of Cardiac Arrhythmias.Journal of arrhythmia · 2022Article
- Liver Cirrhosis Affects the Pharmacokinetics of the Six Substrates of the Basel Phenotyping Cocktail Differently.Clinical pharmacokinetics · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsImpaired liver function often necessitates drug dose adjustment to avoid excessive drug accumulation and adverse events, but a marker for the extent of the required adjustment is lacking. The aim of this study was to investigate whether Child-Pugh (CP) and model for end-stage liver disease (MELD) scores correlate with drug clearance.
methodsMidazolam was used as a CYP3A probe and its pharmacokinetics were analyzed in 24 patients with mild to severe liver cirrhosis (n = 4, 10 and 10 with CP class A, B and C, respectively) and six patients without liver disease.
resultsBoth scores correlated well with unbound midazolam clearance (CLu ), unbound midazolam fraction and half-life (all P < 0.01), whereas the unbound steady-state volume of distribution was not significantly changed. In patients with severe liver cirrhosis unbound midazolam clearance was only 14% of controls (CP C: CLu = 843 ± 346 l h(-1), MELD ≥ 15: CLu = 805 ± 474 l h(-1), controls: CLu = 5815 ± 2649 l h(-1), P < 0.01).
conclusionThe correlation with unbound midazolam clearance suggests that either score predicts the metabolic capacity of CYP3A, the most relevant drug metabolizing enzyme subfamily in humans.
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