Platelet Function: Meloxicam Intravenous in Whole Blood Samples From Healthy Volunteers.
Adenosine Diphosphate
/ metabolism
Administration, Intravenous
Adult
Anti-Inflammatory Agents, Non-Steroidal
/ administration & dosage
Blood Specimen Collection
/ methods
Collagen
/ metabolism
Cyclooxygenase Inhibitors
/ administration & dosage
Drug Compounding
/ methods
Epinephrine
/ metabolism
Female
Healthy Volunteers
/ statistics & numerical data
Hemorrhage
/ chemically induced
Humans
Ketorolac
/ administration & dosage
Male
Meloxicam
/ administration & dosage
Nanoparticles
/ administration & dosage
Pain
/ blood
Platelet Aggregation
/ drug effects
Platelet Function Tests
/ methods
Reagent Kits, Diagnostic
/ standards
anti-inflammatory agents
ketorolac tromethamine
meloxicam
nonsteroidal anti-inflammatory drug
platelet aggregation
Journal
Clinical pharmacology in drug development
ISSN: 2160-7648
Titre abrégé: Clin Pharmacol Drug Dev
Pays: United States
ID NLM: 101572899
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
21
10
2019
accepted:
10
12
2019
pubmed:
22
1
2020
medline:
10
8
2021
entrez:
22
1
2020
Statut:
ppublish
Résumé
Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective treatments for pain but may induce bleeding events due to platelet dysfunction associated with inhibition of cyclooxygenase (COX)-1 impairing thromboxane production. An intravenous nanocrystal formulation of meloxicam, a COX-2 preferential nonsteroidal anti-inflammatory drug, is under development for the treatment of moderate to severe pain. This single-center ex vivo study evaluated the effect of meloxicam intravenous and ketorolac on platelet function in whole blood samples from healthy volunteers. Each whole blood sample was aliquoted to allow analysis using a platelet function analyzer under negative control (untreated), positive control (2 therapeutic ketorolac concentrations), and meloxicam intravenous (1 therapeutic, 3 supratherapeutic concentrations) using both collagen with epinephrine and collagen with adenosine diphosphate reagent cartridges. The platelet function analyzer determines closure time by simulating platelet adhesion and aggregation following vascular injury. The final analysis set included data from 8 subjects. The collagen with adenosine diphosphate analysis (sensitive to thrombocytopathies) showed no significant differences in closure time for meloxicam- or ketorolac-treated samples and untreated control. The collagen with epinephrine analysis (sensitive to aspirin-induced platelet abnormalities) produced no significant difference in closure time between any meloxicam concentration and untreated control. Ketorolac was associated with significantly longer closure times vs untreated control at both the 2.5- and 5-µg/mL concentrations (P = .003 and .0257, respectively) and vs meloxicam at several concentrations. Similar results were observed when all analyzed samples were included. Meloxicam intravenous had no significant effect on closure times at therapeutic or supratherapeutic concentrations in this ex vivo study.
Identifiants
pubmed: 31961516
doi: 10.1002/cpdd.772
pmc: PMC7587000
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Cyclooxygenase Inhibitors
0
Reagent Kits, Diagnostic
0
Adenosine Diphosphate
61D2G4IYVH
Collagen
9007-34-5
Meloxicam
VG2QF83CGL
Epinephrine
YKH834O4BH
Ketorolac
YZI5105V0L
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
841-848Informations de copyright
© 2020 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.
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