ArticleBritish journal of clinical pharmacology2011
Drug-disease interaction: Crohn's disease elevates verapamil plasma concentrations but reduces response to the drug proportional to disease activity.
Article in British journal of clinical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 4 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 4 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Altered Bioavailability and Pharmacokinetics in Crohn's Disease: Capturing Systems Parameters for PBPK to Assist with Predicting the Fate of Orally Administered Drugs.Clinical pharmacokinetics · 2022Pooled it
- Considerations and recommendations for assessment of plasma protein binding and drug-drug interactions for siRNA therapeutics.Nucleic acids research · 2022Pooled it
- Impact of Inflammation on Cytochromes P450 Activity in Pediatrics: A Systematic Review.Clinical pharmacokinetics · 2021Pooled it
- The effect of COX-2-selective meloxicam on the myocardial, vascular and renal risks: a systematic review.Inflammopharmacology · 2015Pooled it
- Drug-Drug Interaction Risk Assessment Strategies for Biologics in Inflammatory Bowel Disease: A Literature-Based Evidence Mini-Review.Clinical and translational science · 2026Review
- Variability in intestinal drug metabolizing enzymes and transporters in Crohn's disease and potential impact on oral drug absorption.British journal of clinical pharmacology · 2025Article
- Dysregulation of the mRNA Expression of Human Renal Drug Transporters by Proinflammatory Cytokines in Primary Human Proximal Tubular Epithelial Cells.Pharmaceutics · 2024Article
- Bounded integer model-based analysis of psoriasis area and severity index in patients with moderate-to-severe plaque psoriasis receiving BI 730357.CPT: pharmacometrics & systems pharmacology · 2023Article
- 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
- 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
- A Mechanistic, Enantioselective, Physiologically Based Pharmacokinetic Model of Verapamil and Norverapamil, Built and Evaluated for Drug-Drug Interaction Studies.Pharmaceutics · 2020Article
- Dose-dependency of the cardiovascular risks of non-steroidal anti-inflammatory drugs.Inflammopharmacology · 2019Article
- Drug-physiology interaction and its influence on the QT prolongation-mechanistic modeling study.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Cardiovascular effect of inflammation and nonsteroidal anti-inflammatory drugs on renin-angiotensin system in experimental arthritis.Inflammopharmacology · 2017Article
- Comparative efficacy of esomeprazole and omeprazole: Racemate to single enantiomer switch.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2015Article
- Pharmacokinetics of Morphine in Rats with Adjuvant-induced Arthritis.In vivo (Athens, Greece)Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimInflammation is involved in the pathogenesis of cardiovascular diseases that includes reduced response to pharmacotherapy due to altered pharmacokinetics and pharmacodynamics. It is not known if these effects exist in general in all inflammatory conditions. It also remains unknown whether in a given population the effect is a function of disease severity. We investigated whether pharmacokinetics and pharmacodynamics of a typical calcium channel inhibitor are influenced by Crohn's disease (CD), a disease for which the disease severity can be readily ranked.
methodsWe administered 80 mg verapamil orally to (i) healthy control subjects (n= 9), (ii) patients with clinically quiescent CD (n= 22) and (iii) patients with clinically active CD (n= 14). Serial analysis of verapamil enantiomers (total and plasma unbound), blood pressure and electrocardiograms were recorded over 8 h post dose. The severity of CD was measured using the Harvey-Bradshaw Index.
resultsCD substantially and significantly increased plasma verapamil concentration and in a stereoselective fashion (S, 9-fold; R, 2-fold). The elevated verapamil concentration, however, failed to result in an increased verapamil pharmacodynamic effect so that the patients with elevated verapamil concentration demonstrated no significant increase in response measured as PR interval and blood pressure. Instead, the greater the disease severity, the lower was the drug potency to prolong PR interval (r= 0.86, P < 0.0006),
conclusionsCD patients with severe disease may not respond to cardiovascular therapy with calcium channel blockers. Reducing the severity increases response despite reduced drug concentration. This observation may have therapeutic implication beyond the disease and the drug studies herein.
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