Transdermal iontophoresis of terazosin: an experimental approach in the treatment of causalgia

Singh, Jatinder Pal (1997) Transdermal iontophoresis of terazosin: an experimental approach in the treatment of causalgia. Masters thesis, Memorial University of Newfoundland.

[English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (4MB)

Abstract

In causalgia (a sympathetic mediated pain syndrome), pain appears to be mediated by the upregulation of α₁ adrenergic receptors on the primary afferents of the peripheral nerves. – Considering the limitations of the existing treatment, it is postulated that an α₁ adrenoreceptor antagonist, terazosin, when delivered locally at a site distal to the nerve injury by transdermal iontophoresis will produce pain relief. Iontophoresis is a noninvasive and a rate controlled drug delivery system. – A sensitive analytical technique for terazosin (TRZ) in plasma was developed using a cyanopropyl solid phase extraction technique and high performance liquid chromatography with fluorescence detection. Analysis of spiked plasma samples indicated no significant differences (p > 0.05) in intra- and inter-day variation. The Solid Phase Extraction (SPE) procedure yielded a complete recovery of TRZ from plasma after an intraperitoneal dose in a rat model. – Results from in vitro and in vivo experiments suggested that the iontophoretic delivery of TRZ was significantly higher than the passive delivery (p < 0.05), and TRZ degradation was prevented by the incorporation of a salt-bridge in the electrode assembly. – It is widely regarded that iontophoresis of small molecular weight ionic compounds have similar pharmacokinetic profile to those administered parenterally. This implies that iontophoresis overcomes the rate limiting barrier (the stratum corneum) and the drug appears in blood immediately following delivery. However, in our studies, peak plasma concentration is reached in approximately 1.5 hours after a ten minute iontophoresis, suggesting a drug depot formation in the skin. The nature (bound/free form) and the exact site of reservoir formation is not yet known. It may be possible to take therapeutic advantage of such a reservoir effect to establish skin depot that is slowly absorbed over time.

Actions (login required)

View Item