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Tytuł:
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The Effect of Verapamil, a P-gp Inhibitor, on the Pharmacokinetics, Safety, and Tolerability of Omadacycline in Healthy Adults: A Phase I, Open-Label, Single-Sequence Study.
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Autorzy:
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Hunt TL; PPD Phase 1 Clinic, 7551 Metro Center Drive, Suite 200, Austin, TX, 78744, USA.
Tzanis E; Paratek Pharmaceuticals, Inc., 1000 First Avenue, Suite 200, King of Prussia, PA, 19406, USA.
Bai S; Paratek Pharmaceuticals, Inc., 1000 First Avenue, Suite 200, King of Prussia, PA, 19406, USA.
Manley A; Paratek Pharmaceuticals, Inc., 1000 First Avenue, Suite 200, King of Prussia, PA, 19406, USA. .
Chitra S; Paratek Pharmaceuticals, Inc., 1000 First Avenue, Suite 200, King of Prussia, PA, 19406, USA.
McGovern PC; Paratek Pharmaceuticals, Inc., 1000 First Avenue, Suite 200, King of Prussia, PA, 19406, USA.
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Źródło:
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European journal of drug metabolism and pharmacokinetics [Eur J Drug Metab Pharmacokinet] 2021 Jan; Vol. 46 (1), pp. 85-92.
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Typ publikacji:
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Clinical Trial, Phase I; Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: <2010- >: Paris : Springer France
Original Publication: Paris, Edifor.
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MeSH Terms:
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Healthy Volunteers*
ATP Binding Cassette Transporter, Subfamily B, Member 1/*antagonists & inhibitors
Anti-Bacterial Agents/*pharmacokinetics
Drug Interactions/*physiology
Tetracyclines/*pharmacokinetics
Verapamil/*pharmacokinetics
Adult ; Anti-Bacterial Agents/administration & dosage ; Humans ; Male ; Middle Aged ; Tetracyclines/administration & dosage ; Verapamil/administration & dosage ; Young Adult
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References:
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Antimicrob Agents Chemother. 2015 Nov;59(11):7044-53. (PMID: 26349824)
Bioorg Med Chem. 2016 Dec 15;24(24):6409-6419. (PMID: 27469981)
Xenobiotica. 2017 Aug;47(8):682-696. (PMID: 27499331)
Antimicrob Agents Chemother. 2016 Nov 21;60(12):7431-7435. (PMID: 27736760)
Future Microbiol. 2016 Oct;11:1421-1434. (PMID: 27539442)
Lancet Infect Dis. 2019 Oct;19(10):1080-1090. (PMID: 31474458)
Eur J Pharm Sci. 2018 Mar 30;115:339-344. (PMID: 29391214)
Clin Pharmacokinet. 1984 Jan-Feb;9(1):26-41. (PMID: 6362951)
Clin Infect Dis. 2019 Aug 1;69(Suppl 1):S16-S22. (PMID: 31367744)
N Engl J Med. 2019 Feb 7;380(6):517-527. (PMID: 30726692)
Clin Infect Dis. 2019 Aug 1;69(Suppl 1):S23-S32. (PMID: 31367742)
Antimicrob Agents Chemother. 2018 Jan 25;62(2):. (PMID: 29158281)
Eur J Drug Metab Pharmacokinet. 1985 Apr-Jun;10(2):133-8. (PMID: 3840089)
Drug Metab Dispos. 2005 Mar;33(3):426-33. (PMID: 15608139)
Antimicrob Agents Chemother. 2018 Jan 25;62(2):. (PMID: 29180524)
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Substance Nomenclature:
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0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
0 (Anti-Bacterial Agents)
0 (Tetracyclines)
090IP5RV8F (omadacycline)
CJ0O37KU29 (Verapamil)
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Entry Date(s):
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Date Created: 20201112 Date Completed: 20210923 Latest Revision: 20210923
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Update Code:
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20240105
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PubMed Central ID:
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PMC7811981
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DOI:
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10.1007/s13318-020-00651-3
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PMID:
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33180250
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Background: Omadacycline is a semisynthetic aminomethylcycline antibacterial derived from the tetracycline class. It is approved in the USA to treat adults with acute bacterial skin and skin-structure infections and community-acquired bacterial pneumonia.
Objectives: This phase I, open-label study evaluated the effect of a potential drug-drug interaction of verapamil-a known P-glycoprotein (P-gp) inhibitor-with omadacycline on the pharmacokinetic profile of omadacycline in healthy adults. The safety and tolerability of omadacycline taken alone and in combination with verapamil were also evaluated.
Methods: A single oral dose of 240 mg verapamil extended release (ER) was given 2 h prior to a single oral dose of 300 mg omadacycline.
Results: Ten (83.3%) of the 12 participants enrolled in the study completed the study, and all enrolled participants were included in the safety and pharmacokinetic populations. An increase of 14-25% in systemic exposure to omadacycline was seen when administered following a single oral dose of 240 mg verapamil ER compared with omadacycline alone, as measured by the area under the concentration-time curve (AUC) from time 0 to 24 h after dosing (AUC 0-24 ), from time 0 to the last quantifiable concentration (AUC 0-t ), from time 0 extrapolated to infinity (AUC 0-inf ), and by maximum (peak) observed plasma concentration (C max ). Treatment-emergent adverse events were reported by one participant (nausea and headache).
Conclusions: These findings suggest that, if given with a known P-gp inhibitor, dose adjustment of oral omadacycline is not warranted based on small increases in absorption and systemic exposure. No safety signals were identified.