title: Effect of Physiological Changes in the Skin on Systemic Absorption of Tacrolimus Following Topical Application in Rats.
abstract: Tacrolimus (TL) ointment is a topical treatment for atopic dermatitis, a disease that exhibits various skin conditions. The effect of skin pathologies on the systemic absorption of TL and related side effects remains unknown. This study aimed to investigate factors affecting the cutaneous absorption of TL. We prepared various skin models in hairless rats by tape stripping, injection of prophlogistic material solution (PMS), and continuous subcutaneous adrenaline (Adr) infusion. In vivo absorption studies were conducted, with measurements of transepidermal water loss (TEWL) and skin blood flow as physiological parameters. Very little TL absorption was observed through intact skin. Greater TL absorption was noted in skins with high TEWL values and fully stripped skin with PMS injections. In contrast, Adr infusion, which reduced skin blood flow, resulted in decreased TL absorption through fully stripped skin. Combined use of TL and Adr on skin with PMS injections resulted in suppression of TL absorption. Our results revealed that TL absorption following topical application is affected by alterations in the skin barrier, blood flow, and vascular permeability. We propose an administration plan for TL in a flowchart as a means of preventing systemic side effects.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Hazama
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Maekawa
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Miki
authors.forename: Shinji
authors.initials: S
authors.lastname: Oshima
authors.forename: Yuya
authors.initials: Y
authors.lastname: Egawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Morimoto
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Seki
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D054772:Rats, Hairless; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects; D012879:Skin Physiological Phenomena / Q000187:drug effects; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus; D004837:Epinephrine