ReviewBritish journal of pharmacology2009
To scale or not to scale: the principles of dose extrapolation.
Review in British journal of pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04020419 (Natural Berry Extract Treatment of Hemangiomas), which is not on this map. Cited by 223 papers, 6 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Natural Berry Extract Treatment of Hemangiomas
Who cites it
223 citing papers in PubMed, 6 syntheses or guidelines pooled it, 528 citations in OpenAlex.
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- Adjuvant therapies for management of hemorrhagic shock: a narrative review.Critical care (London, England) · 2025Pooled it
- The effects ofFrontiers in nutrition · 2025Pooled it
- Determination of the starting dose in the first-in-human clinical trials with monoclonal antibodies: a systematic review of papers published between 1990 and 2013.Drug design, development and therapy · 2016Pooled it
- Pilot study evaluating tolerability and changes in fecal microbiota associated with novel probiotic administration to dogs with diarrhea.Frontiers in veterinary science · 2025Trial
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- Predicting Efavirenz Concentrations in the Brain Tissue of HIV-Infected Individuals and Exploring their Relationship to Neurocognitive Impairment.Clinical and translational science · 2019Trial
- Pharmacokinetics of a Transdermal Fentanyl Solution in Suffolk Sheep (Journal of the American Association for Laboratory Animal Science : JAALAS · 2017Trial
- Population Pharmacokinetics of Pyronaridine in Pediatric Malaria Patients.Antimicrobial agents and chemotherapy · 2015Trial
- Single oral dose pharmacokinetics of decursin and decursinol angelate in healthy adult men and women.PloS one · 2015Trial
- Metabolic fate and detectability of three novel fluoroprolintane psychostimulants: in vitro and in vivo characterization by hyphenated mass spectrometry.Archives of toxicology · 2026Article
- Physiologically based pharmacokinetic modeling to predict human pharmacokinetics of a novel mithramycin analog for Ewing sarcoma.Cancer chemotherapy and pharmacology · 2026Article
- First-in-Human Dose Selection, Pharmacokinetics Prediction, and Clinical Validation of SYHA1805, a Novel FXR Agonist, Using Allometric Scaling and PBPK Modeling.Pharmaceutics · 2026Article
- Beyond Body Weight: A Comprehensive Review of Allometric Scaling in Drug Development for Human Dose Predictions.Pharmaceutics · 2026Review
- Integrated Study of Vancomycin-Induced Nephrotoxicity in the Context of Sepsis: Animal Models and Transcriptomics.Kidney360 · 2026Article
- Scientific Opinion on waiving of the dog studies in the regulatory process of agrochemicals approval.EFSA journal. European Food Safety Authority · 2026Article
- Neural stem cell delivery of oncolytic CRAd-S-pk7 immunotherapy for stage 3 ovarian cancer: Dose-regimen studies.Molecular therapy. Oncology · 2026Article
- In Vivo mRNA-Lipid Nanoparticle CAR-T Cell Engineering: Advances, Challenges, and Clinical Translation.Biomedicines · 2026Review
163 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The principles of inter-species dose extrapolation are poorly understood and applied. We provide an overview of the principles underlying dose scaling for size and dose adjustment for size-independent differences. Scaling of a dose is required in three main situations: the anticipation of first-in-human doses for clinical trials, dose extrapolation in veterinary practice and dose extrapolation for experimental purposes. Each of these situations is discussed. Allometric scaling of drug doses is commonly used for practical reasons, but can be more accurate when one takes into account species differences in pharmacokinetic parameters (clearance, volume of distribution). Simple scaling of drug doses can be misleading for some drugs; correction for protein binding, physicochemical properties of the drug or species differences in physiological time can improve scaling. However, differences in drug transport and metabolism, and in the dose-response relationship, can override the effect of size alone. For this reason, a range of modelling approaches have been developed, which combine in silico simulations with data obtained in vitro and/or in vivo. Drugs that are unlikely to be amenable to simple allometric scaling of their clearance or dose include drugs that are highly protein-bound, drugs that undergo extensive metabolism and active transport, drugs that undergo significant biliary excretion (MW > 500, ampiphilic, conjugated), drugs whose targets are subject to inter-species differences in expression, affinity and distribution and drugs that undergo extensive renal secretion. In addition to inter-species dose extrapolation, we provide an overview of dose extrapolation within species, discussing drug dosing in paediatrics and in the elderly.
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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.