title: Application of in vivo microdialysis to transdermal absorption of methotrexate in rats.
abstract: Microdialysis was applied to determine the in vivo transdermal absorption of methotrexate (MTX) in rats with or without a new penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101). A solution composed of 2.5 mM MTX and 3% (w/v) HPE-101 was applied to the shaved abdomen, in which a semipermeable membrane cannula of 10-mm length was inserted intracutaneously with the use of an L-shaped needle. Intradermal microdialysis was performed at a flow rate of 1.0 microL/min for 12 hr. The concentration of MTX in the dialysate was measured by fluorescence polarization immunoassay (FPIA). HPE-101 (3%, w/v) significantly increased the dermal MTX concentration from 0.06 +/- 0.04 microM in the control to 56 +/- 26 microM in the dialysate from 8 to 12 hr. HPE-101 at concentrations of 0.75, 1.5, 2.25, and 3% (w/v) enhanced the total recovery of MTX in dermal dialysate from 0 to 10 hr by approximately 5, 18, 42, and 500 times compared with the control, respectively. The microdialysis system is useful for assessing in vivo transdermal drug absorption.
authors.affiliation: Department of Hospital Pharmacy, School of Medicine, Nagasaki University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsuyama
authors.forename: M
authors.initials: M
authors.lastname: Nakashima
authors.forename: Y
authors.initials: Y
authors.lastname: Nakaboh
authors.forename: M
authors.initials: M
authors.lastname: Ichikawa
authors.forename: T
authors.initials: T
authors.lastname: Yano
authors.forename: S
authors.initials: S
authors.lastname: Satoh
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D004337:Drug Carriers; D016231:Fluorescence Polarization Immunoassay; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017551:Microdialysis; D011758:Pyrroles; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000502:physiology*
chemical_list: D004337:Drug Carriers; D011758:Pyrroles; C075725:1-(2-(decylthio)ethyl)azacyclopentane-2-one; D008727:Methotrexate