ReviewPhilosophical transactions of the Royal Society of London. Series B, Biological sciences2014
Comparative metabolism as a key driver of wildlife species sensitivity to human and veterinary pharmaceuticals.
Review in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 75 citations in OpenAlex.
- Evaluation of Human-Approved Active Pharmaceutical Ingredients Against Lactate Dehydrogenase from Theileria annulata.Acta parasitologica · 2026Article
- Tracing Veterinary Pharmaceuticals through Regurgitated Pellets: A Noninvasive Monitoring Approach to Assess Exposure in Avian Scavengers.Environmental science & technology · 2026Article
- Article
- Cocktails of NSAIDs and 17α Ethinylestradiol at Environmentally Relevant Doses in Drinking Water Alter Puberty Onset in Mice Intergenerationally.International journal of molecular sciences · 2023Article
- Effect of cytochrome P450 inhibition on toxicity of diclofenac in chickens: Unravelling toxicity in Gyps vultures.The Onderstepoort journal of veterinary research · 2022Article
- A Critical Review of the Pharmacokinetics, Pharmacodynamics, and Safety Data of Antibiotics in Avian Species.Antibiotics (Basel, Switzerland) · 2022Review
- Swine as the Animal Model for Testing New Formulations of Anti-Inflammatory Drugs: Carprofen Pharmacokinetics and Bioavailability of the Intramuscular Route.Pharmaceutics · 2022Article
- Pharmacokinetics of the Anti-Inflammatory Drug Meloxicam after Single 1.5 mg/kg Intramuscular Administration to Undulate Skates (Veterinary sciences · 2022Article
- Article
- Response of Two Crop Plants,International journal of molecular sciences · 2021Article
- Article
- Characterization of In Vitro and In Vivo Metabolism of Antazoline Using Liquid Chromatography-Tandem Mass Spectrometry.International journal of molecular sciences · 2020Article
- The Role of Omics in the Application of Adverse Outcome Pathways for Chemical Risk Assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2017Review
- Practical approaches to adverse outcome pathway development and weight-of-evidence evaluation as illustrated by ecotoxicological case studies.Environmental toxicology and chemistry · 2017Review
- Metabolism and Disposition of Aditoprim in Swine, Broilers, Carp and Rats.Scientific reports · 2016Article
- Medicating the environment: assessing risks of pharmaceuticals to wildlife and ecosystems.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2014Article
- Leveraging existing data for prioritization of the ecological risks of human and veterinary pharmaceuticals to aquatic organisms.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2014Review
- Medicines, shaken and stirred: a critical review on the ecotoxicology of pharmaceutical mixtures.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2014Review
- Assessing variation in the potential susceptibility of fish to pharmaceuticals, considering evolutionary differences in their physiology and ecology.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2014Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human and veterinary drug development addresses absorption, distribution, metabolism, elimination and toxicology (ADMET) of the Active Pharmaceutical Ingredient (API) in the target species. Metabolism is an important factor in controlling circulating plasma and target tissue API concentrations and in generating metabolites which are more easily eliminated in bile, faeces and urine. The essential purpose of xenobiotic metabolism is to convert lipid-soluble, non-polar and non-excretable chemicals into water soluble, polar molecules that are readily excreted. Xenobiotic metabolism is classified into Phase I enzymatic reactions (which add or expose reactive functional groups on xenobiotic molecules), Phase II reactions (resulting in xenobiotic conjugation with large water-soluble, polar molecules) and Phase III cellular efflux transport processes. The human-fish plasma model provides a useful approach to understanding the pharmacokinetics of APIs (e.g. diclofenac, ibuprofen and propranolol) in freshwater fish, where gill and liver metabolism of APIs have been shown to be of importance. By contrast, wildlife species with low metabolic competency may exhibit zero-order metabolic (pharmacokinetic) profiles and thus high API toxicity, as in the case of diclofenac and the dramatic decline of vulture populations across the Indian subcontinent. A similar threat looms for African Cape Griffon vultures exposed to ketoprofen and meloxicam, recent studies indicating toxicity relates to zero-order metabolism (suggesting P450 Phase I enzyme system or Phase II glucuronidation deficiencies). While all aspects of ADMET are important in toxicity evaluations, these observations demonstrate the importance of methods for predicting API comparative metabolism as a central part of environmental risk assessment.
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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.