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

Autor: Zhang QL; Department of Pharmacy, General Hospital of Lanzhou Command of PLA, Lanzhou 730050, People's Republic of China. zhangquanlong@hotmail.com, Hu JH, Jia ZP, Wang D, Zhu QG
Jazyk: angličtina
Zdroj: Biomedical chromatography : BMC [Biomed Chromatogr] 2012 May; Vol. 26 (5), pp. 622-6. Date of Electronic Publication: 2011 Dec 02.
DOI: 10.1002/bmc.1707
Abstrakt: 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 C(max) 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 C(max) 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 T(max) , 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.)
Databáze: MEDLINE
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