ReviewBritish journal of clinical pharmacology2016
The law of mass action and the pharmacological concentration-effect curve: resolving the paradox of apparently non-dose-related adverse drug reactions.
Review in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The relationship between dose and serotonin transporter occupancy of antidepressants-a systematic review.Molecular psychiatry · 2022Pooled it
- Penicillin allergy de-labelling in the critical care unit: Simulations to design an intravenous drug provocation test that mirrors the plasma profile of an enteral challenge.British journal of clinical pharmacology · 2026Article
- Potential Drug Dose-Specific Adverse Three-Drug Combinations: A US Insurance Claims Data-Based Study.Pharmacoepidemiology and drug safety · 2025Article
- A Method for in Situ Interfacial pH Detection.The journal of physical chemistry letters · 2025Article
- Enemies or Allies? Hormetic and Apparent Non-Dose-Dependent Effects of Natural Bioactive Antioxidants in the Treatment of Inflammation.International journal of molecular sciences · 2024Review
- Acute Oral Toxicological Profile ofJournal of toxicology · 2024Article
- What I have learnt from helping thousands of people taper off antidepressants and other psychotropic medications.Therapeutic advances in psychopharmacology · 2021Review
- Nobody ever questions-Polypharmacy in care homes: A mixed methods evaluation of a multidisciplinary medicines optimisation initiative.PloS one · 2021Article
- Susceptibility to adverse drug reactions.British journal of clinical pharmacology · 2019Review
- New Insights in Computational Methods for Pharmacovigilance:International journal of environmental research and public health · 2019Article
- Adverse Drug Reactions, Power, Harm Reduction, Regulation and the ADRe Profiles.Pharmacy (Basel, Switzerland) · 2018Article
- Ailanthone inhibits non-small cell lung cancer cell growth through repressing DNA replication via downregulating RPA1.British journal of cancer · 2017Article
- Pharmacogenomics of off-target adverse drug reactions.British journal of clinical pharmacology · 2017Review
- The law of mass action and the pharmacological concentration-effect curve: resolving the paradox of apparently non-dose-related adverse drug reactions.British journal of clinical pharmacology · 2016Review
- A web resource for mining HLA associations with adverse drug reactions: HLA-ADR.Database : the journal of biological databases and curation · 2016Article
- Classifying ADRs--does dose matter?British journal of clinical pharmacology · 2016Article
- Cato Guldberg and Peter Waage, the history of the Law of Mass Action, and its relevance to clinical pharmacology.British journal of clinical pharmacology · 2016Review
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAdverse drug reactions are sometimes described as being 'non-dose-related' because no relationship has been found between increasing doses and either the intensity of the response or the proportion of individuals in whom the response occurs; furthermore, hypersensitivity reactions are often regarded as being non-dose-related, even if different doses have not been studied. However, the law of mass action implies that all pharmacological effects are concentration related and should increase in intensity with increasing dose. We set out to explain this paradox.
methodsWe searched for published adverse drug reactions that have been described as non-dose-related and analysed them.
resultsWe identified four categories of explanations that resolve the paradox: (i) the reaction is not real; it may have occurred by chance or there may be methodological problems, such as bias or confounding factors; (ii) the dose-response curve for the adverse effect reaches a maximum at doses lower than were studied (i.e. a hypersusceptibility reaction); this underpins the use of test doses to predict the possibility of an adverse reaction at therapeutic doses; (iii) susceptibility to the adverse reaction differs widely among individuals; and (iv) imprecision or inaccuracy in the measurement of either dose or effect obscures dose responsiveness. This last explanation encompasses: (a) reactions related to cumulative dose; (b) dissociation between dose and concentration through saturable pharmacokinetics; and (c) variability in the measurement of the effect. CONCLUSIONS AND IMPLICATIONS: If an adverse drug reaction appears to be non-dose-related, the reasons should be sought, having these mechanisms in mind.
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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.