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Effect of heparin administration on flunitrazepam protein binding
R Calvo1, L Aguilera, C Aguirre
1Department of Pharmacology, University of Basque Country, Leioa, Vizcaya, Spain.
Summary
Free fatty acids significantly decrease flunitrazepam binding to plasma proteins. This finding is crucial for understanding drug interactions and flunitrazepam
Area of Science:
- Pharmacology
- Biochemistry
- Clinical Chemistry
Background:
- Non-esterified fatty acids displace diazepam from plasma binding sites.
- Lorazepam binding is unaffected by free fatty acids.
- Flunitrazepam shows significant plasma protein binding.
Purpose of the Study:
- To investigate the effect of free fatty acids on flunitrazepam binding to human plasma proteins.
Main Methods:
- In vitro incubation of plasma with sodium oleate.
- In vivo administration of sodium heparin to increase free fatty acid levels.
- Measurement of flunitrazepam free fraction in plasma.
Main Results:
- Sodium oleate decreased flunitrazepam binding, increasing its free fraction.
- Heparin administration increased free fatty acids and flunitrazepam free fraction.
- A direct relationship was observed between free fatty acid concentration and flunitrazepam's unbound fraction.
Conclusions:
- Increased free fatty acid concentrations reduce the plasma protein binding of flunitrazepam.
- These findings highlight a potential drug interaction mechanism involving free fatty acids and flunitrazepam.