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Xenobiotica
the fate of foreign compounds in biological systems
Volume 53, 2023 - Issue 8-9
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Animal Pharmacokinetics and Metabolism

Evobrutinib pathway to its major metabolite M463-2 and insights from a biotransformation and DDI perspective

Holger Scheiblea NCE DMPK Merck Healthcare KGaA, Darmstadt, GermanyCorrespondence[email protected]
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,
Hanno Schiefersteina NCE DMPK Merck Healthcare KGaA, Darmstadt, GermanyView further author information
,
Ralf Schmidtb EMD Serono Research & Development Institute, Inc, Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, GermanyView further author information
,
Klaus Puseckera NCE DMPK Merck Healthcare KGaA, Darmstadt, GermanyView further author information
,
Ulrike Gradhanda NCE DMPK Merck Healthcare KGaA, Darmstadt, GermanyView further author information
,
Sathej Gopalakrishnanc Quantitative Pharmacology Merck Healthcare KGaA, Darmstadt, GermanyView further author information
,
Khalid Iqbalc Quantitative Pharmacology Merck Healthcare KGaA, Darmstadt, GermanyView further author information
,
Jennifer Dongb EMD Serono Research & Development Institute, Inc, Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, GermanyView further author information
,
Reinaldo Jonesb EMD Serono Research & Development Institute, Inc, Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, GermanyView further author information
,
Claudia Melid Merck Ltd, Piedmont, Italy, an affiliate of Merck KGaA, Darmstadt, GermanyView further author information
,
Jayaprakasam Bolleddulab EMD Serono Research & Development Institute, Inc, Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, GermanyView further author information
,
Martin Dyroffb EMD Serono Research & Development Institute, Inc, Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, GermanyView further author information
&
Katrin Georgia NCE DMPK Merck Healthcare KGaA, Darmstadt, GermanyView further author information
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Pages 547-558 | Received 15 Aug 2023, Accepted 14 Oct 2023, Published online: 25 Oct 2023

References

  • Bender AT, Gardberg A, Pereira A, Johnson T, Wu Y, Grenningloh R, Head J, Morandi F, Haselmayer P, Liu-Bujalski L. 2017. Ability of Bruton’s tyrosine kinase inhibitors to sequester Y551 and prevent phosphorylation determines potency for inhibition of Fc receptor but not B-cell receptor signaling. Mol Pharmacol. 91(3):208–219. doi: 10.1124/mol.116.107037.
  • Bertilsson L, Tomson T. 1986. Clinical pharmacokinetics and pharmacological effects of carbamazepine and carbamazepine-10,11-epoxide. An update. Clin Pharmacokinet. 11(3):177–198. doi: 10.2165/00003088-198611030-00001.
  • Caldwell RD, Qiu H, Askew BC, Bender AT, Brugger N, Camps M, Dhanabal M, Dutt V, Eichhorn T, Gardberg AS, et al. 2019. Discovery of Evobrutinib: an oral, potent, and highly selective, covalent Bruton’s tyrosine kinase (BTK) inhibitor for the treatment of immunological diseases. J Med Chem. 62(17):7643–7655. doi: 10.1021/acs.jmedchem.9b00794.
  • Carnero Contentti E, Correale J. 2022. Current perspectives: evidence to date on BTK inhibitors in the management of multiple sclerosis. Drug Des Devel Ther. 16:3473–3490. doi: 10.2147/DDDT.S348129.
  • Cencioni MT, Mattoscio M, Magliozzi R, Bar-Or A, Muraro PA. 2021. B cells in multiple sclerosis – from targeted depletion to immune reconstitution therapies. Nat Rev Neurol. 17(7):399–414. doi: 10.1038/s41582-021-00498-5.
  • Cheng Y, Prusoff WH. 1973. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol. 22(23):3099–3108. doi: 10.1016/0006-2952(73)90196-2.
  • Coelho MM, Fernandes C, Remião F, Tiritan ME. 2021. Enantioselectivity in drug pharmacokinetics and toxicity: pharmacological relevance and analytical methods. Molecules. 26(11):3113. doi: 10.3390/molecules26113113.
  • Coppola P, Andersson A, Cole S. 2019. The importance of the human mass balance study in regulatory submissions. CPT Pharmacometrics Syst Pharmacol. 8(11):792–804. doi: 10.1002/psp4.12466.
  • EMA-ICH. 2013. ICH guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals. [accessed 2023 January 24]. https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-m3r2-non-clinical-safety-studies-conduct-human-clinical-trials-marketing-authorisation_en.pdf.
  • FDA. 2020. Safety testing of drug metabolites guidance for industry. [accessed 2023 January 24]. https://www.fda.gov/media/72279/download.
  • Haselmayer P, Camps M, Liu-Bujalski L, Nguyen N, Morandi F, Head J, O'Mahony A, Zimmerli SC, Bruns L, Bender AT, et al. 2019. Efficacy and pharmacodynamic modeling of the BTK inhibitor Evobrutinib in autoimmune disease models. J Immunol. 202(10):2888–2906. doi: 10.4049/jimmunol.1800583.
  • ICH. 2022. ICH harmonised guideline – drug interaction studies M12. https://database.ich.org/sites/default/files/M12_Step1_draft_Guideline_2022_0524.pdf.
  • Li R, Tang H, Burns JC, Hopkins BT, Le Coz C, Zhang B, de Barcelos IP, Romberg N, Goldstein AC, Banwell BL, et al. 2022. BTK inhibition limits B-cell-T-cell interaction through modulation of B-cell metabolism: implications for multiple sclerosis therapy. Acta Neuropathol. 143(4):505–521. doi: 10.1007/s00401-022-02411-w.
  • López-Herrera G, Vargas-Hernández A, González-Serrano ME, Berrón-Ruiz L, Rodríguez-Alba JC, Espinosa-Rosales F, Santos-Argumedo L. 2014. Bruton’s tyrosine kinase–an integral protein of B cell development that also has an essential role in the innate immune system. J Leukoc Biol. 95(2):243–250. doi: 10.1189/jlb.0513307.
  • Njuguna NM, Umehara KI, Huth F, Schiller H, Chibale K, Camenisch G. 2016. Improvement of the chemical inhibition phenotyping assay by cross-reactivity correction. Drug Metab Pers Ther. 31(4):221–228.
  • Scheible H, Dyroff M, Seithel-Keuth A, Harrison-Moench E, Mammasse N, Port A, Bachmann A, Dong J, van Lier JJ, Tracewell W, et al. 2021. Evobrutinib, a covalent Bruton’s tyrosine kinase inhibitor: mass balance, elimination route, and metabolism in healthy participants. Clin Transl Sci. 14(6):2420–2430. doi: 10.1111/cts.13108.
  • Shah V, Yang C, Shen Z, Kerr BM, Tieu K, Wilson DM, Hall J, Gillen M, Lee CA. 2019. Metabolism and disposition of Lesinurad, a uric acid reabsorption inhibitor, in humans. Xenobiotica. 49(7):811–822. doi: 10.1080/00498254.2018.1504257.

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