Trial reportEuropean journal of clinical pharmacology2013
Influence of chronic hepatitis C infection on cytochrome P450 3A4 activity using midazolam as an in vivo probe substrate.
Trial report in European journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Raltegravir pharmacokinetics before and during treatment with ombitasvir, paritaprevir/ritonavir plus dasabuvir in adults with human immunodeficiency virus-1 and hepatitis C virus coinfection: AIDS Clinical Trials Group sub-study A5334s.British journal of clinical pharmacology · 2020Trial
- Oxysterols as Biomarkers of Aging and Disease.Advances in experimental medicine and biology · 2024Article
- Comparison and summary of in silico prediction tools for CYP450-mediated drug metabolism.Drug discovery today · 2023Review
- The Role of CYP3A in Health and Disease.Biomedicines · 2022Review
- Pre-procedural Preparation and Sedation for Gastrointestinal Endoscopy in Patients with Advanced Liver Disease.Digestive diseases and sciences · 2022Review
- Benign course of residual inflammation at end of treatment of liver transplant recipients after sofosbuvir based therapy.World journal of hepatology · 2022Article
- Inflammation Induces Changes in the Functional Expression of P-gp, BCRP, and MRP2: An Overview of Different Models and Consequences for Drug Disposition.Pharmaceutics · 2021Review
- 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
- Inflammation is a major regulator of drug metabolizing enzymes and transporters: Consequences for the personalization of drug treatment.Pharmacology & therapeutics · 2020Review
- Cytochrome P450-mediated drug interactions in COVID-19 patients: Current findings and possible mechanisms.Medical hypotheses · 2020Article
- A Pharmacology Perspective of Simultaneous Tuberculosis and Hepatitis C Treatment.Antimicrobial agents and chemotherapy · 2019Review
- Impact of direct-acting antivirals for hepatitis C virus therapy on tacrolimus dosing in liver transplant recipients.Transplant infectious disease : an official journal of the Transplantation Society · 2019Article
- Oxysterols and Gastrointestinal Cancers Around the Clock.Frontiers in endocrinology · 2019Review
- Article
- Population Pharmacokinetic Analysis of Asunaprevir in Subjects with Hepatitis C Virus Infection.Infectious diseases and therapy · 2018Article
- Drug-Drug Interactions with the NS3/4A Protease Inhibitor Simeprevir.Clinical pharmacokinetics · 2016Review
- Asunaprevir: A Review of Preclinical and Clinical Pharmacokinetics and Drug-Drug Interactions.Clinical pharmacokinetics · 2015Review
- Effect of hepatitis B and C clearance on atazanavir exposure.European journal of clinical pharmacology · 2015Article
- Molecular docking to understand the metabolic behavior of GNF-351 by CYP3A4 and its potential drug-drug interaction with ketoconazole.European journal of drug metabolism and pharmacokinetics · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeInflammation-related changes in pharmacokinetics have been described for a number of disease-states including cancer, infection, and autoimmune disorders. This study examined the impact of chronic hepatitis C infection (CHC) on the pharmacokinetics of the cytochrome P450 3A probe midazolam in patients without significant liver disease who were either treatment naïve or prior interferon null-responders.
methodsData were pooled from three studies which compared the pharmacokinetics of oral midazolam in healthy volunteers (n = 107) and in treatment-naive patients (n = 35) and interferon-null responders (n = 24) with CHC but without significant liver disease. Oral midazolam was administered as a single 2 mg oral dose, followed by frequent pharmacokinetic sampling and determination of the pharmacokinetics of midazolam and its α-hydroxy metabolite. CYP3A activity was determined by the metabolic ratio (MR) of the AUC metabolite/AUC parent and compared across groups as the mean effect ratio (test/reference).
resultsThe midazolam MR was lower in treatment-naïve patients with CHC than in health volunteers with a mean effect ratio of 0.63 [90 % confidence interval (CI) 0.56-0.72]. The effect was more pronounced in null-responders, who demonstrated a mean MR effect ratio of 0.46 (90 % CI 0.39-0.53) compared to volunteers. The mean area under the concentration-time curve (AUCinf) for midazolam in healthy volunteers, naïve patients, and null-responders was 32.3 [coefficient of variation (CV%) 41], 36.5 (CV% 33.5), and 55.3 (CV% 36.9) ng.h/mL, respectively.
conclusionsThe results of this study demonstrate a reduction in CYP3A4 activity between healthy volunteers and patients with CHC, with interferon null-responders demonstrating the most substantial difference. These results may have implications for the pharmacotherapy of patients infected with CHC.
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