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.
Eur J Drug Metab Pharmacokinet
; 46(1): 85-92, 2021 Jan.
Article
em En
| MEDLINE
| ID: mdl-33180250
ABSTRACT
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 (AUC0-24), from time 0 to the last quantifiable concentration (AUC0-t), from time 0 extrapolated to infinity (AUC0-inf), and by maximum (peak) observed plasma concentration (Cmax). 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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Tetraciclinas
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Verapamil
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Interações Medicamentosas
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Voluntários Saudáveis
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Antibacterianos
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Drug Metab Pharmacokinet
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos