ArticleDrug metabolism and disposition: the biological fate of chemicals2019
Absolute Quantitation of Drug-Metabolizing Cytochrome P450 Enzymes and Accessory Proteins in Dog Liver Microsomes Using Label-Free Standard-Free Analysis Reveals Interbreed Variability.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 37 citations in OpenAlex.
- High-level expression of full-length human CYP2E1 in Escherichia coli: Comparison of full-length human CYP2E1 to truncated counterpart shows enhanced association with redox partners.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Canine duodenal organoids as a functional platform for intestinal CYP regulation and drug metabolism studies.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Evaluation of the relationship between cytochrome P450 (CYP) 1A2 gene copy number variation and CYP1A2 protein content and enzyme activity in canine liver.Frontiers in veterinary science · 2025Article
- Article
- Interlaboratory Variability in the Madin-Darby Canine Kidney Cell Proteome.Molecular pharmaceutics · 2023Article
- Metabolism of ropinirole is mediated by several canine CYP enzymes.Veterinary medicine and science · 2023Article
- Specific Gene Duplication and Loss of Cytochrome P450 in Families 1-3 in Carnivora (Mammalia, Laurasiatheria).Animals : an open access journal from MDPI · 2022Article
- Comparison of Canine and Human Physiological Factors: Understanding Interspecies Differences that Impact Drug Pharmacokinetics.The AAPS journal · 2021Review
- Identification and characterization of the enzymes responsible for the metabolism of the non-steroidal anti-inflammatory drugs, flunixin meglumine and phenylbutazone, in horses.Journal of veterinary pharmacology and therapeutics · 2021Article
- Sequencing of the Canine Cytochrome P450 CYP2C41 Gene and Genotyping of Its Polymorphic Occurrence in 36 Dog Breeds.Frontiers in veterinary science · 2021Article
- Pharmacokinetics and Safety of Mitragynine in Beagle Dogs.Planta medica · 2020Article
- Pharmacogenomics of poor drug metabolism in Greyhounds: Cytochrome P450 (CYP) 2B11 genetic variation, breed distribution, and functional characterization.Scientific reports · 2020Article
- Adverse Drug-Drug Interaction Between Phenobarbital and Fluconazole in Two Dogs.Journal of veterinary internal medicineArticle
- The effect of concurrent clopidogrel and omeprazole administration on clopidogrel metabolism and platelet function in healthy cats.Journal of veterinary internal medicineArticle
- Amphipol-facilitated elucidation of the functional tetrameric complex of full-length cytochrome P450 CYP2B4 and NADPH-cytochrome P450 oxidoreductase.The Journal of biological chemistryArticle
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Dogs are commonly used in human and veterinary pharmaceutical development. Physiologically based pharmacokinetic modeling using recombinant cytochrome P450 (CYP) enzymes requires accurate estimates of CYP abundance, particularly in liver. However, such estimates are currently available for only seven CYPs, which were determined in a limited number of livers from one dog breed (beagle). In this study, we used a label-free shotgun proteomics method to quantitate 11 CYPs (including four CYPs not previously measured), cytochrome P450 oxidoreductase, and cytochrome b5 in liver microsomes from 59 dogs representing four different breeds and mixed-breed dogs. Validation included showing correlation with CYP marker activities, immunoquantified protein, as well as CYP1A2 and CYP2C41 null allele genotypes. Abundance values largely agreed with those previously published. Average CYP abundance was highest (>120 pmol/mg protein) for CYP2D15 and CYP3A12; intermediate (40-89 pmol/mg) for CYP1A2, CYP2B11, CYP2E1, and CYP2C21; and lowest (<12 pmol/mg) for CYP2A13, CYP2A25, CYP2C41, CYP3A26, and CYP1A1. The CYP2C41 gene was detected in 12 of 58 (21%) livers. CYP2C41 protein abundance averaged 8.2 pmol/mg in those livers, and was highest (19 pmol/mg) in the only liver with two CYP2C41 gene copies. CYP1A2 protein was not detected in the only liver homozygous for the CYP1A2 stop codon mutation. Large breed-associated differences were observed for CYP2B11 (
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