ArticlePharmaceutical research2012
Mass spectrometry-based quantification of CYP enzymes to establish in vitro/in vivo scaling factors for intestinal and hepatic metabolism in beagle dog.
Article in Pharmaceutical research, 2012. 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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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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Who cites it
15 citing papers in PubMed, 35 citations in OpenAlex.
- Physiologically based pharmacokinetic modelling to predict single- and multiple-dose human pharmacokinetics of bitopertin.Clinical pharmacokinetics · 2013Trial
- Overlooked aspects of scaling enzyme activity through abundance across tissues and individuals: Insights from kDrug 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
- Assessment of cytochrome P450 induction in canine intestinal organoid models.Xenobiotica; the fate of foreign compounds in biological systems · 2024Article
- Interlaboratory Variability in the Madin-Darby Canine Kidney Cell Proteome.Molecular pharmaceutics · 2023Article
- Comparison of Canine and Human Physiological Factors: Understanding Interspecies Differences that Impact Drug Pharmacokinetics.The AAPS journal · 2021Review
- Parameterization of Microsomal and Cytosolic Scaling Factors: Methodological and Biological Considerations for Scalar Derivation and Validation.European journal of drug metabolism and pharmacokinetics · 2021Article
- Absolute Quantitation of Drug-Metabolizing Cytochrome P450 Enzymes and Accessory Proteins in Dog Liver Microsomes Using Label-Free Standard-Free Analysis Reveals Interbreed Variability.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Kinetics of Cyclophosphamide Metabolism in Humans, Dogs, Cats, and Mice and Relationship to Cytotoxic Activity and Pharmacokinetics.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Simultaneous absolute quantitation of ATP-binding cassette transporters in normal dog tissues by signature peptide analysis using a LC/MS/MS method.Research in veterinary science · 2019Article
- Microsomal and Cytosolic Scaling Factors in Dog and Human Kidney Cortex and Application for In Vitro-In Vivo Extrapolation of Renal Metabolic Clearance.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Quantifying gut wall metabolism: methodology matters.Biopharmaceutics & drug disposition · 2017Article
- Predicting Drug Extraction in the Human Gut Wall: Assessing Contributions from Drug Metabolizing Enzymes and Transporter Proteins using Preclinical Models.Clinical pharmacokinetics · 2016Review
- Quantitative ADME proteomics - CYP and UGT enzymes in the Beagle dog liver and intestine.Pharmaceutical research · 2015Article
- Canine cytochrome P-450 pharmacogenetics.The Veterinary clinics of North America. Small animal practice · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposePhysiologically based models, when verified in pre-clinical species, optimally predict human pharmacokinetics. However, modeling of intestinal metabolism has been a gap. To establish in vitro/in vivo scaling factors for metabolism, the expression and activity of CYP enzymes were characterized in the intestine and liver of beagle dog.
methodsMicrosomal protein abundance in dog tissues was determined using testosterone-6β-hydroxylation and 7-hydroxycoumarin-glucuronidation as markers for microsomal protein recovery. Expressions of 7 CYP enzymes were estimated based on quantification of proteotypic tryptic peptides using multiple reaction monitoring mass spectrometry. CYP3A12 and CYP2B11 activity was evaluated using selective marker reactions.
resultsThe geometric mean of total microsomal protein was 51 mg/g in liver and 13 mg/cm in intestine, without significant differences between intestinal segments. CYP3A12, followed by CYP2B11, were the most abundant CYP enzymes in intestine. Abundance and activity were higher in liver than intestine and declined from small intestine to colon.
conclusionsCYP expression in dog liver and intestine was characterized, providing a basis for in vitro/in vivo scaling of intestinal and hepatic metabolism.
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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.