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Increased vigabatrin entry into the brain by polysorbate 80 and sodium caprate
D Dimitrijevic1, P S Whitton, M Domin
1Centre for Drug Delivery Research, The School of Pharmacy, University of London, UK.
The Journal of Pharmacy and Pharmacology
|March 29, 2001
Summary
Polysorbate 80 and sodium caprate enhanced vigabatrin brain absorption in rats, increasing gamma-aminobutyric acid (GABA) levels. These enhancers also amplified vigabatrin-induced hypothermia, suggesting improved brain penetration.
Area of Science:
- Neuroscience and Pharmacology
- Drug Delivery and Formulation
Background:
- Vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid (GABA) transaminase, increasing brain GABA concentrations.
- Enhancing brain penetration of vigabatrin could improve its therapeutic efficacy.
- Polysorbate 80 (non-ionic surfactant) and sodium caprate (fatty acid salt) were investigated as potential brain absorption enhancers.
Purpose of the Study:
- To evaluate the efficacy of polysorbate 80 and sodium caprate as enhancers for vigabatrin brain absorption.
- To quantify the impact of these enhancers on brain GABA concentrations in vivo.
- To assess the effect of vigabatrin and enhancers on rat body temperature as an indicator of brain penetration.
Main Methods:
- Non-toxic concentrations of surfactants were determined using the red blood cell lysis test.
- Vigabatrin was administered intravenously to Wistar rats, with and without enhancers (polysorbate 80 or sodium caprate).
- Brain concentrations of vigabatrin and GABA were measured using selected ion monitoring electrospray mass spectrometry.
- Rectal temperature was monitored as a physiological indicator.
Main Results:
- While vigabatrin alone caused a small increase in brain GABA, co-administration with polysorbate 80 or sodium caprate resulted in significantly higher GABA levels.
- Analysis of variance confirmed a significant effect of the surfactants on brain GABA concentrations (P < 0.01).
- Vigabatrin administration decreased rectal temperature; this hypothermic effect was significantly amplified when vigabatrin was given with either enhancer (P < 0.001).
Conclusions:
- Polysorbate 80 and sodium caprate effectively enhance vigabatrin brain absorption in rats, as evidenced by increased brain GABA levels.
- The enhanced hypothermic response further supports improved vigabatrin penetration into the brain when co-administered with these enhancers.
- These surfactants show promise as excipients for improving the brain delivery of vigabatrin.