Iontophoretic transdermal delivery of ketoprofen: effect of iontophoresis on drug transfer from skin to cutaneous blood.
The objectives of this study were to develop a method for kinetic analysis of drug transfer to cutaneous blood flow and to evaluate the effect of iontophoresis on drug transfer to cutaneous blood. Cathodal iontophoresis of ketoprofen (non-steroidal anti-inflammatory drug) was conducted to rats (applied electrical current 0.14 and 0.70 mA/cm2; application time 5, 15, 30, 60 and 90 min), and the drug concentrations in skin, cutaneous vein and systemic vein were determined. Transfer rate of ketoprofen from skin to cutaneous blood (R(SC)) was calculated by modifying a physiological pharmacokinetic model. The time-course of R(SC) for 0.70 mA/cm2 showed that the value of R(SC) was initially increased, following a gradual decrease with time after 30-min application. The effect of electrical current on drug transfer to cutaneous blood flow was estimated from the comparison to passive diffusion (without electrical current). The R(SC) value at 30-min application was almost proportional to the electrical current, and the enhancement ratio for 0.14 and 0.70 mA/cm2 was 17 and 73, respectively. Consequently, our results suggest that the change of drug transfer to cutaneous blood flow by iontophoresis may depend on the application period and the magnitude of electrical current.
Tashiro
Y
Y
Drug Formulation Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Sunto-gun, Shizuoka, Japan. yoshikazu.tashiro@kyowa.co.jp
Kato
Y
Y
Hayakawa
E
E
Ito
K
K
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D001783:Blood Flow Velocity / Q000502:physiology; D007478:Iontophoresis; D007660:Ketoprofen / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply*; D012869:Skin Absorption / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007660:Ketoprofen