Effect of vasoactive agents on the dermatopharmacokinetics and systemic disposition of model compounds, salicylate and FITC-dextran 4 kDa, following intracutaneous injection of the compounds.
The effects of two vasoactive agents, phenylephrine and tolazoline, were determined on the dermatopharmacokinetics and systemic disposition of model compounds, salicylate (SA) and FITC-dextran 4 kDa (FD-4), following their intracutaneous (i.c.) injection. The determined blood flow in skin was lowered and increased by i.c. injection of phenylephrine and tolazoline, respectively. Dermatopharmacokinetics and the systemic disposition of SA and FD-4 with and without vasoactive agents were analyzed using a compartment model. As a result, the rate constant, k(sc), from skin to systemic circulation of SA after i.c. injection with phenylephrine was almost zero, and the rate constant, k(sm), from skin to muscle increased about 2.4-fold compared with the control group (without vasoactive agents). In contrast, the rate constants, k(sc) and k(sm), after i.c. injection of SA with tolazoline were increased about 1.9- and 2.5-fold, respectively, compared with the control. In FD-4 disposition, k(sc) and k(sm) decreased to about 0.3-fold and increased to about 4.0-fold compared with the control after i.c. injection with phenylephrine. The k(sc) and k(sm) of FD-4 increased with tolazoline about 2.2- and 4.3-fold compared with the control, respectively. These data suggest that these vasoactive agents can be used to modify the dermatopharmacokinetics of topically or intracutaneously applied drugs.
Yoshida
Daisuke
D
Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
Todo
Hiroaki
H
Hasegawa
Tetsuya
T
Sugibayashi
Kenji
K
D000818:Animals; D003911:Dextrans / Q000493:pharmacokinetics*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007271:Injections, Intradermal; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply / Q000378:metabolism; D012869:Skin Absorption; D012980:Sodium Salicylate / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014043:Tolazoline / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D003911:Dextrans; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C015219:fluorescein isothiocyanate dextran; D010656:Phenylephrine; D014043:Tolazoline; D016650:Fluorescein-5-isothiocyanate; D012980:Sodium Salicylate