Pharmacokinetics of aconitine in rat skin after oral and transdermal gel administrations

Abstract

The purpose of this study was to evaluate percutaneous penetration and arrhythmogenic effects of aconitine after transdermal administration, compared with the oral route. Skin penetration of aconitine was tested by a microdialysis technique in rats and in vivo recovery was determined by retrodialysis. After oral and transdermal administration of aconitine, dialysate was sampled at 20 min intervals until the end of the experiment for the determination of concentration of aconitine in skin. Blood samples were collected and analyzed using a validated HPLC‐MS/MS method. In addition, we concurrently recorded the electrocardiogram (ECG). The in vivo recovery of aconitine in the skin was calculated to be 39.59%. The Cmax values for aconitine absorbed into the skin after oral and transdermal administration were 1.51 ± 0.53 and 2723.8 ± 848.8 ng/mL, respectively, and within the plasma, 215.86 ± 79.29 and 20.92 ± 3.15 ng/mL. The Cmax value for the plasma concentration of aconitine after oral administration was approximately 10 times higher than with the transdermal route. For oral administration, the ECG revealed various types of arrhythmias at a period of Tmax, which is normal in transdermal gel administration. These results indicate that transdermal aconitine gel is a safe formulation that can deliver the drug in sufficient amounts and safe concentrations to produce therapeutic action in rats. Copyright © 2011 John Wiley & Sons, Ltd.

Visualizing Dermal Permeation of Sodium Channel Modulators by Mass Spectrometric Imaging

“…Transdermal permeation experiments using live murine subjects were performed for comparative purposes against ex Vivo data. Solutions of aconitine and STX-ge in either ethanol or DMSO were applied to the shaved back of male Sprague–Dawley rats under general anesthesia (see Supporting Information for experimental details) . The animals were sacrificed, their skin removed, sectioned, and analyzed following the same experimental procedures used for ex vivo experiments.…”

“…Solutions of aconitine and STX-ge in either ethanol or DMSO were applied to the shaved back of male Sprague−Dawley rats under general anesthesia (see Supporting Information for experimental details). 28 The animals were sacrificed, their skin removed, sectioned, and analyzed following the same experimental procedures used for ex vivo experiments. Pathologic evaluation of the tissue sections revealed that in all samples analyzed, besides skin epidermis, dermis, and hypodermis layers, muscle tissue was also present.…”

Percutaneous absorption effects of Chinese herbal medicine

“…There have been more and more reports on efficacy of transdermal patch in treating both human and animal diseases (Plosker, 2011;Zhang et al, 2011;Dou et al, 2011). Use of Chinese Herbal Medicine (CHM) as transdermal agents is a new combination of Traditional Chinese Medicine (TCM) with modern pharmaceutical technology (He et al, 2009;Qian et al, 2011).…”