Permeability of nitroimidazoles in rat cortex

Area of Science:

• Neuroscience
• Pharmacology
• Biomedical Engineering

Background:

• Nitroimidazole drugs are used as antibiotics.
• Understanding their transport into the brain is crucial for effective treatment.
• Current methods for assessing brain drug penetration can be limited.

Purpose of the Study:

• To evaluate cerebrovascular permeability of nitroimidazole drugs in rats.
• To introduce microvoltammetry as a novel technique for studying drug transfer in the brain.
• To correlate drug properties with their ability to cross the blood-brain barrier.

Main Methods:

• In situ perfusion of the rat right cerebral hemisphere via the external carotid artery.
• Retrograde bolus infusion of nitroimidazole drugs.
• Continuous measurement of drug concentrations in brain cortex using microvoltammetric electrodes.
• Simultaneous measurement of drug concentrations in blood samples using high-performance liquid chromatography.

Main Results:

• Cerebrovascular permeability coefficients for six nitroimidazoles were determined.
• Coefficients ranged from 0.8 x 10^-4 to 3 x 10^-6 cm/s.
• Drug permeability was directly proportional to their octanol-water partition coefficient.

Conclusions:

• Microvoltammetry is a viable new method for studying cerebrovascular transfer of electroactive drugs in rats.
• Drug lipophilicity, indicated by the octanol-water partition coefficient, influences brain penetration.
• This technique can aid in the development of antibiotics targeting the central nervous system.