Convolution method to predict drug concentration profiles of 2,3,5,6-tetramethylpyrazine following transdermal application.
The objective of this work is to predict the systemic drug concentration of 2,3,5,6-tetramethylpyrazine (TMP) following transdermal application in rabbits from the in vitro skin permeation data. The in vitro skin permeation was studied in Franz diffusion cells. Pharmacokinetic evaluation of TMP following transdermal application and bolus intravenous administration were carried out in New Zealand White (NZW) rabbits. Drug concentration-time curve following transdermal application was predicted via the convolution procedure using an in vitro skin permeation data as a weighting function, and the intravenous data as an unit impulse response. The results showed that the predicted drug concentration following transdermal application by convolution method was in good agreement with the observed drug absorption profiles. These findings indicated that in vitro skin permeation tests could be useful to predict in vivo drug absorption profiles following transdermal application.
Qi
Xiaohong
X
Global Product Development, Worldwide Consumer Medicines, Bristol-Myers Squibb Company, 1350 Liberty Avenue, Hillside, NJ 07111, USA. xiaohong.qi@bms.com
Liu
Rong Ron
RR
Sun
Duxin
D
Ackermann
Chrisita
C
Hou
Huimin
H
D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008954:Models, Biological; D010539:Permeability; D011719:Pyrazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption
D011719:Pyrazines; C017953:tetramethylpyrazine