nism in cross-hypersensitivity to NSAIDs and, consequently, will add to the controversy in the mechanisms underlying the development of cross-hypersensitivity to NSAIDs. The key clinical implication of our findings is that we located no proof supporting the utility of preemptive CYP2C genotyping aiming at drug selection for patients having a prior history of cross-hypersensitivity to NSAIDs. Nevertheless, the findings obtained in this study usually do not rule out the possible of pharmacogenetics testing combined with phenotyping aspects and testing for other genes involved in NSAID pharmacodynamics and/or genes involved in the improvement and also the clinical presentation with the hypersensitivity reactions, such as genes related to the TLR8 drug arachidonic acid pathway, at the same time as those related to inflammation mediators, and oxidative stress.Information AVAILABILITY STATEMENTThe datasets presented in this study may be found in on the web repositories. The names on the repository/repositories and accession quantity(s) could be located inside the article/Supplementary Material.ETHICS STATEMENTThe research involving human participants were reviewed and approved by the Badajoz University Hospital, M aga University Hospital, Madrid Cruz Roja Hospital, Barcelona Clinic Hospital, Madrid Infanta Leonor Hospital, Alcorc University Hospital, and Elche University Hospital. The patients/participants supplied their written informed consent to take part in this study.Frontiers in Pharmacology | frontiersin.orgSeptember 2021 | Volume 12 | ArticleMac s et al.CYP2C Variants in NSAIDs Cross-HypersensitivityAUTHOR CONTRIBUTIONSAuthor contribution statement: All authors have created substantial contributions as follows: Study design: EG-M and JA. Manuscript Drafting: YM, EG-M and JA. Genotyping analyses: YM, EG-M, and JA. Statistical analyses MM, YM, and JA. Patient recruitment and clinical evaluation: JG-M, CC, RJ-E, JC-G, MT, NB-L, GC, MB, JL, JB, AR, and JF. All authors gave final approval from the version to be published. All authors agreed to become accountable for all aspects in the operate.Investigaci Sanitaria, Instituto de Salud Carlos III, Madrid, Spain, and IB16170, IB20134 and GR18145 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Union.ACKNOWLEDGMENTSWe are grateful to Prof. James McCue for his help in language editing.SUPPLEMENTARY MATERIAL FUNDINGThis function was partly supported by Grants PI15/00303, PI18/00540, and RETICS ARADyAL RD16/0006/0004 from Fondo de The Supplementary Material for this short article might be identified on the net at: frontiersin.org/articles/10.3389/fphar.2021.648262/ full#supplementary-materialwith Paclitaxel 6alpha-Hydroxylase Activity in Human Liver Microsomes. Biochem. Pharmacol. 64 (11), 1579589. doi:10.1016/s0006-2952(02)01354-0 Bakhriansyah, M., Meyboom, R. H. B., Souverein, P. C., de Boer, A., and Nav1.6 custom synthesis Klungel, O. H. (2019). Cyclo-oxygenase Selectivity and Chemical Groups of Nonsteroidal Antiinflammatory Drugs and also the Frequency of Reporting Hypersensitivity Reactions: a Case/noncase Study in VigiBase. Fundam. Clin. Pharmacol. 33 (5), 58900. doi:ten.1111/fcp.12463 Benjamini, Y., Drai, D., Elmer, G., Kafkafi, N., and Golani, I. (2001). Controlling the False Discovery Rate in Behavior Genetics Research. Behav. Brain Res. 125 (1), 27984. doi:ten.1016/s0166-4328(01)00297-2 Bigler, J., Whitton, J., Lampe, J. W., Fosdick, L., Bostick, R. M., and Potter, J. D. (2001). CYP2C9 and UGT1A6 Genotypes Modulate the Protective Impact of Aspirin on colon Adeno