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      Effects of CYP1A enzyme specific inhibitor on pharmacokinetics of para-acetaminophen in Bactrian camel

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          Abstract

          The effects of CYP1A enzyme on the pharmacokinetics of p-acetaminophen were studied in Bactrian camel. Twelve Bactrian camels were divided into 2 groups, then given a single dose of p-acetaminophen only or with the enzyme inhibitor lomefloxacin. Blood samples were collected after different intervals, and p-acetaminophen concentration was determined by high-performance liquid chromatography. Pharmacokinetic parameters were analyzed by Phoenix WinNonLin v.7.0. The results show that lomefloxacin can significantly inhibit Bactrian camel CYP1A enzyme, as evidenced by the prolonged elimination half-life, increased maximum plasma conce[INSERT FIGURE 001]ntration and area under the curve values and the shortened time to peak concentration for p-acetaminophenol in the substrate with inhibitor group. The results lay a foundation for revealing the particular characteristics of the CYP1A enzyme in Bactrian camels.

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          Variation in CYP1A2 activity and its clinical implications: influence of environmental factors and genetic polymorphisms.

          Arzu Gunes, Marja-Liisa Dahl (2008)
          CYP1A2 is involved in the metabolism of several widely used drugs and endogenous compounds, and in the activation of procarcinogens. Both genetic and environmental factors influence the activity of this enzyme. The current knowledge regarding factors influencing the activity of CYP1A2 is summarized in this review. Substrates, inhibitors and inducers of CYP1A2 activity, as well as phenotyping probes, are discussed. The functional significance and clinical importance of CYP1A2 gene polymorphisms are reviewed and interethnic differences in the distribution of CYP1A2 variant alleles and haplotypes are summarized. Finally, future perspectives for the possible clinical applications of CYP1A2 genotyping are discussed.
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            Measurement of CYP1A2 activity: a focus on caffeine as a probe.

            Vidya Perera, Annette Gross, Andrew McLachlan (2012)
            The drug metabolising enzyme CYP1A2 contributes to the metabolism of a number of medicines including clozapine, olanzapine and theophylline. These medicines display a high degree of inter-individual variability in pharmacokinetics and response. Measuring CYP1A2 activity in vivo can be an important tool to identify the factors that influence variability in drug pharmacokinetics and inform dose selection. Caffeine is the only currently accepted probe to conduct in vivo phenotyping of CYP1A2. Despite the number of proposed matrices (biological fluid containing the drug and/or metabolite/s of interest) and metrics (mathematical formula relating the drug and/or metabolite/s to enzyme activity) proposed to measure CYP1A2 activity using caffeine, many of these are compromised by factors related to the specific metabolic pathway studied or pharmacokinetic characteristics of caffeine and its metabolites. Furthermore, questions regarding the appropriate study design and methodology to conduct studies to evaluate CYP1A2 activity have often been overlooked. These issues include the potential influence of a methylxanthine abstinence period prior to caffeine CYP1A2 phenotyping and the impact of caffeine formulation on determining CYP1A2 activity. This review aims to discuss the various CYP1A2 matrices and metrics with a particular focus on unresolved methodological issues.
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              Human genetic variation of CYP450 superfamily: analysis of functional diversity in worldwide populations.

              Renato Polimanti, Sara Piacentini, Dario Manfellotto … (2012)
              The present study aimed to investigate the human genetic diversity of the CYP450 superfamily in order to identify functional interethnic differences and analyze the role of CYP450 enzymes in human adaptation.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Vet Sci
                Journal ID (iso-abbrev): J. Vet. Sci
                Journal ID (publisher-id): JVS
                Title: Journal of Veterinary Science
                Publisher: The Korean Society of Veterinary Science
                ISSN (Print): 1229-845X
                ISSN (Electronic): 1976-555X
                Publication date (Print): May 2019
                Publication date (Electronic): 15 March 2019
                Volume: 20
                Issue: 3
                Electronic Location Identifier: e12
                Affiliations
                [1 ]College of Veterinary Medicine, Inner Mongolia Agricultural University/Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, Hohhot 010018, China.
                [2 ]Inner Mongolia institute of Camel Research, Badain Jaran 750300, China.
                Author notes
                Corresponding author: Surong Hasi. College of Veterinary Medicine, Inner Mongolia Agricultural University/Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, No. 306, Zhaowuda Road, Saihan District, Hohhot 010018, China. surong@ 123456imau.edu.cn
                Author information
                https://orcid.org/0000-0002-8252-7150
                https://orcid.org/0000-0002-7128-6849
                Article
                DOI: 10.4142/jvs.2019.20.e12
                PMC ID: 6538516
                SO-VID: 5e307a28-4ae8-468f-a248-3419ac092eba
                Copyright © © 2019 The Korean Society of Veterinary Science
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 30 November 2018
                Date revision received : 31 January 2019
                Date accepted : 08 February 2019
                Funding
                Funded by: National Natural Science Foundation of China, CrossRef https://doi.org/10.13039/501100001809;
                Award ID: 31560710
                Award ID: 31260623
                Categories
                Subject: Short Communication

                ScienceOpen disciplines: Veterinary medicine
                Keywords: bactrian camel,cyp1a,substrate,pharmacokinetics,inhibitor
                Data availability:
                ScienceOpen disciplines: Veterinary medicine
                Keywords: bactrian camel, cyp1a, substrate, pharmacokinetics, inhibitor

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