ArticleClinical pharmacokinetics2022
Liver Cirrhosis Affects the Pharmacokinetics of the Six Substrates of the Basel Phenotyping Cocktail Differently.
Article in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03337945 (In Vivo Determination of Cytochrome P450 Activities in Patients With Liver Cirrhosis), which is not on this map. Cited by 22 papers.
What it found
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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.
In Vivo Determination of Cytochrome P450 Activities in Patients With Liver Cirrhosis
Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
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- Inflammation-driven variability in drug metabolism: Insights from voriconazole treatment of HSCT recipients.British journal of clinical pharmacology · 2026Article
- Physiological and Anatomical Alterations in Children with Liver Cirrhosis.Pharmaceutical research · 2026Review
- Effects of Opioids, Benzodiazepines, Gabapentinoids, and Antidepressants on Fracture Risk in Alcohol-Related Cirrhosis.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Comprehensive Pathophysiology Repository for PBPK Modeling in Liver Cirrhosis: Quantifying Continuous Disease Progression and Population Variability.CPT: pharmacometrics & systems pharmacology · 2026Article
- Pharmacokinetics of CYP2C19- and CYP3A4-Metabolized Drugs in Cirrhosis Using a Whole-Body PBPK Approach.Pharmaceutics · 2025Article
- Arachidonic acid metabolism in metabolic dysfunction-associated steatotic liver disease and liver fibrosis.Hepatology communications · 2025Review
- Combining endoscopic variceal ligation and omeprazole sodium in treating upper gastrointestinal hemorrhage combined with liver cirrhosis.BMC gastroenterology · 2025Article
- Donafenib intolerance in hepatocellular carcinoma: severe hand-foot skin reaction and successful switch to lenvatinib - a case report and literature review.Frontiers in oncology · 2025Article
- New Insights Into Hepatic Impairment (HI) Trials.Clinical and translational science · 2025Review
- Phenoconversion andHepatology forum · 2025Review
- Improving Individualized Salbutamol Treatment: A Population Pharmacokinetic Model for Oral Salbutamol in Virtual Patients.Pharmaceutics · 2024Article
- Phase 1 pharmacokinetic and safety study of soticlestat in participants with mild or moderate hepatic impairment or normal hepatic function.Pharmacology research & perspectives · 2024Article
- Decoding the Role of CYP450 Enzymes in Metabolism and Disease: A Comprehensive Review.Biomedicines · 2024Review
- Simultaneously Predicting the Pharmacokinetics of CES1-Metabolized Drugs and Their Metabolites Using Physiologically Based Pharmacokinetic Model in Cirrhosis Subjects.Pharmaceutics · 2024Article
- Exogenous Volatile Organic Compound (EVOCBiomedicines · 2023Article
- Hepatic Impairment as a Risk Factor for Drug Safety: Suitability and Comparison of Four Liver Scores as Screening Tools.Journal of clinical medicine · 2023Article
- The Activity of Members of the UDP-Glucuronosyltransferase Subfamilies UGT1A and UGT2B is Impaired in Patients with Liver Cirrhosis.Clinical pharmacokinetics · 2023Article
- Pharmacokinetic and Pharmacodynamic Drug-Drug Interactions: Research Methods and Applications.Metabolites · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundActivities of hepatic cytochrome P450 enzymes (CYPs) are relevant for hepatic clearance of drugs and known to be decreased in patients with liver cirrhosis. Several studies have reported the effect of liver cirrhosis on CYP activity, but the results are partially conflicting and for some CYPs lacking.
objectiveIn this study, we aimed to investigate the CYP activity in patients with liver cirrhosis with different Child stages (A-C) using the Basel phenotyping cocktail approach.
methodsWe assessed the pharmacokinetics of the six compounds and their CYP-specific metabolites of the Basel phenotyping cocktail (CYP1A2: caffeine, CYP2B6: efavirenz, CYP2C9: flurbiprofen, CYP2C19: omeprazole, CYP2D6: metoprolol, CYP3A: midazolam) in patients with liver cirrhosis (n = 16 Child A cirrhosis, n = 15 Child B cirrhosis, n = 5 Child C cirrhosis) and matched control subjects (n = 12).
resultsWhile liver cirrhosis only marginally affected the pharmacokinetics of the low to moderate extraction drugs efavirenz and flurbiprofen, the elimination rate of caffeine was reduced by 51% in patients with Child C cirrhosis. For the moderate to high extraction drugs omeprazole, metoprolol, and midazolam, liver cirrhosis decreased the elimination rate by 75%, 37%, and 60%, respectively, increased exposure, and decreased the apparent systemic clearance (clearance/bioavailability). In patients with Child C cirrhosis, the metabolic ratio (ratio of the area under the plasma concentration-time curve from 0 to 24 h of the metabolite to the parent compound), a marker for CYP activity, decreased by 66%, 47%, 92%, 73%, and 43% for paraxanthine/caffeine (CYP1A2), 8-hydroxyefavirenz/efavirenz (CYP2B6), 5-hydroxyomeprazole/omeprazole (CYP2C19), α-hydroxymetoprolol/metoprolol (CYP2D6), and 1'-hydroxymidazolam/midazolam (CYP3A), respectively. In comparison, the metabolic ratio 4-hydroxyflurbiprofen/flurbiprofen (CYP2C9) remained unchanged.
conclusionsLiver cirrhosis affects the activity of CYP isoforms differently. This variability must be considered for dose adjustment of drugs in patients with liver cirrhosis. CLINICAL
trial registrationNCT03337945.
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