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      Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of New Anti-Migraine Drugs—Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies

      review-article
      Pharmaceutics
      MDPI
      migraine, lasmiditan, gepants, monoclonal antibodies, drug–drug interactions

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          Abstract

          In the last few years, there have been significant advances in migraine management and prevention. Lasmiditan, ubrogepant, rimegepant and monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) are new drugs that were launched on the US pharmaceutical market; some of them also in Europe. This publication reviews the available worldwide references on the safety of these anti-migraine drugs with a focus on the possible drug–drug (DDI) or drug–food interactions. As is known, bioavailability of a drug and, hence, its pharmacological efficacy depend on its pharmacokinetics and pharmacodynamics, which may be altered by drug interactions. This paper discusses the interactions of gepants and lasmiditan with, i.a., serotonergic drugs, CYP3A4 inhibitors, and inducers or breast cancer resistant protein (BCRP) and P-glycoprotein (P-gp) inhibitors. In the case of monoclonal antibodies, the issue of pharmacodynamic interactions related to the modulation of the immune system functions was addressed. It also focuses on the effect of monoclonal antibodies on expression of class Fc gamma receptors (FcγR).

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          Most cited references125

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          SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

          Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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            Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition

            (2018)
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              • Record: found
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              • Article: not found

              A Controlled Trial of Erenumab for Episodic Migraine

              We tested erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, for the prevention of episodic migraine.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                03 December 2020
                December 2020
                : 12
                : 12
                : 1180
                Affiliations
                Department of Clinical Pharmacy and Biopharmacy, Poznań University of Medical Sciences, Św. Marii Magdaleny 14 St., 61-861 Poznań, Poland; dszkutnik@ 123456ump.edu.pl
                Author information
                https://orcid.org/0000-0002-1856-1733
                Article
                pharmaceutics-12-01180
                10.3390/pharmaceutics12121180
                7761673
                33287305
                e891a21c-66a5-44bc-baac-8fc2f4b4a155
                © 2020 by the author.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 October 2020
                : 30 November 2020
                Categories
                Review

                migraine,lasmiditan,gepants,monoclonal antibodies,drug–drug interactions

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