Trial reportBritish journal of clinical pharmacology2000
Decreased dromotropic response to verapamil despite pronounced increased drug concentration in rheumatoid arthritis.
Trial report in British journal of clinical pharmacology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- Considerations and recommendations for assessment of plasma protein binding and drug-drug interactions for siRNA therapeutics.Nucleic acids research · 2022Pooled it
- Lack of Effect of 12-Week Treatment with Risankizumab on the Pharmacokinetics of Cytochrome P450 Probe Substrates in Patients with Moderate to Severe Chronic Plaque Psoriasis.Clinical pharmacokinetics · 2019Trial
- Influence of chronic hepatitis C infection on cytochrome P450 3A4 activity using midazolam as an in vivo probe substrate.European journal of clinical pharmacology · 2013Trial
- Trial
- Evaluation of the Effect of Risankizumab on the Pharmacokinetics of Cytochrome P450 Substrates in Patients with Moderately to Severely Active Ulcerative Colitis or Crohn's Disease.Clinical pharmacokinetics · 2025Article
- Applications of the Cholesterol Metabolite, 4β-Hydroxycholesterol, as a Sensitive Endogenous Biomarker for Hepatic CYP3A Activity Evaluated within a PBPK Framework.Pharmaceutics · 2024Article
- The Impact of Paediatric Obesity on Drug Pharmacokinetics: A Virtual Clinical Trials Case Study with Amlodipine.Pharmaceutics · 2024Article
- Advancing personalized medicine for tuberculosis through the application of immune profiling.Frontiers in cellular and infection microbiology · 2023Review
- Drug-disease interaction: Clinical consequences of inflammation on drugs action and disposition.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2023Review
- 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
- Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature.Frontiers in pharmacology · 2021Review
- Cytochrome P450-mediated drug interactions in COVID-19 patients: Current findings and possible mechanisms.Medical hypotheses · 2020Article
- Inflammation is a major regulator of drug metabolizing enzymes and transporters: Consequences for the personalization of drug treatment.Pharmacology & therapeutics · 2020Review
- Impact of Interleukin-6 on Drug-Metabolizing Enzymes and Transporters in Intestinal Cells.The AAPS journal · 2019Article
- Altered cytochrome 2E1 and 3A P450-dependent drug metabolism in advanced ovarian cancer correlates to tumour-associated inflammation.British journal of pharmacology · 2019Article
- Cardiorenal Safety of OTC Analgesics.Journal of cardiovascular pharmacology and therapeutics · 2018Review
- Cardiovascular effect of inflammation and nonsteroidal anti-inflammatory drugs on renin-angiotensin system in experimental arthritis.Inflammopharmacology · 2017Article
- 4β-Hydroxycholesterol Level in Patients With Rheumatoid Arthritis Before vs. After Initiation of bDMARDs and Correlation With Inflammatory State.Clinical and translational science · 2017Observational
- Drug disposition in pathophysiological conditions.Current drug metabolism · 2012Review
- Immunological response as a source to variability in drug metabolism and transport.Frontiers in pharmacology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsInflammation reduces hepatic clearance of many drugs with unknown therapeutic consequences. This study was carried out to examine the effect of rheumatoid arthritis (RA) on the pharmacokinetics and pharmacodynamics of verapamil.
methodsEight RA patients were age- and sex-matched with eight healthy volunteers. The disease severity was assessed, and ECG, blood pressure and verapamil enantiomers concentrations were measured for 12 h post 80 mg oral verapamil. Serum interleukin-6 (IL-6) and nitrite (NO2-) were measured in predose samples.
resultsIL-6 and NO2- concentrations were significantly increased in parallel with disease severity. Oral clearance of both S- and R-verapamil was significantly decreased by RA. While the unbound fraction of S- and R-verapamil decreased by 5 and 7-fold, respectively, the unbound AUC remained unchanged for the more potent enantiomer, S-verapamil. AUC of norverapamil enantiomers was increased 2-3-fold. Despite elevated serum drug concentrations in RA, the potential to prolong the PR-interval was significantly reduced by one fold and the effect on the heart rate and blood pressure did not increase.
conclusionsRA results in increased verapamil concentrations due likely to changes in protein binding, decreased clearance and/or altered hepatic blood flow. A significant decrease in dromotropic effect, despite increased serum drug concentrations, may be attributed to receptor down regulation caused by pro-inflammatory cytokines and/or NO.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.