Extraction of levetiracetam for therapeutic drug monitoring by transdermal reverse iontophoresis

Abstract Recently, transdermal reverse iontophoresis across the skin has been investigated as a novel technology for the purpose of diagnosis as well as therapeutic drug monitoring. Accordingly, the objective of this study was to investigate ex vivo and in vivo transdermal extraction of levetiracetam, an antiepileptic drug, across the pig ear skin by reverse iontophoresis. Reverse iontophoresis experiments were performed using three chambered diffusion cells. Extractions profiles were generated in phosphate buffers at different current intensities, pH and ionic strength as well donor drug concentrations. This was followed by ex vivo extraction in gels and in vivo extractions using New Zealand rabbits. Results indicate that levetiracetam was extracted at both anode and cathode. Flux values were unaffected by increase in current intensities (0.5 mA and 0.6 mA) but affected by pH and ionic strength. Neither in cathodal nor in anodal extraction, flux values did show a proportional relationship with the donor drug concentration. At low and medium concentration levels, flux values did not show any major change but the extraction flux at high donor concentration was much higher. In contrast, in vivo experiment with rabbits resulted in wide variation of fluxes with very high fluxes recorded at the cathodal end. Reasons attributed to this difference may include lower current intensity, and species variation. The most significant finding of this study is that measurable amounts of the levetiracetam were extracted at both the ends indicating its feasibility for non-invasive drug monitoring.