title: Topical formulations containing finasteride. Part I: in vitro permeation/penetration study and in vivo pharmacokinetics in hairless rat.
abstract: In hair follicle (Hf) cells, the type-2 5-α-reductase enzyme, implicated in androgenetic alopecia, is selectively inhibited by finasteride (FNS). Because an effective topical formulation to deliver FNS to Hf is currently unavailable, this investigation aimed at evaluating in vitro FNS skin permeation and retention through and into hairless rat and human abdominal skin. Four hydroxypropyl chitosan (HPCH)-based formulations (P-08-012, P-08-016, P-08-063, and P-08-064) and one anhydrous formulation without HPCH (P-10-008) were tested. The pharmacokinetics in plasma and skin after application of P-08-016 or P-10-008 on dorsal rat skin with single and repeated doses was investigated. P-08-016 performed the best in driving FNS to the reticular dermis without producing a high transdermal flux. Neither the in vivo single nor the repeated dose experiments produced plasma levels of FNS and no differences were found between formulations concerning skin retention. No increase in the amount of drug retained in the skin was obtained with the repeated dose experiment. In conclusion, the HPCH-based formulation P-08-016 might represent an alternative to systemic therapy for its ability to promote a cutaneous depot of FNS in the region of hair bulbs, minimizing systemic absorption even after repeated treatments.
authors.affiliation: Department of Pharmacy, University of Pisa, Pisa, I-56126, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.forename: Silvia
authors.initials: S
authors.lastname: Tampucci
authors.forename: Susi
authors.initials: S
authors.lastname: Burgalassi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Chetoni
authors.forename: Carla
authors.initials: C
authors.lastname: Lenzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Pirone
authors.forename: Federico
authors.initials: F
authors.lastname: Mailland
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000279:Administration, Cutaneous; D000505:Alopecia / Q000188:drug therapy; D000818:Animals; D018120:Finasteride / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D051381:Rats; D054772:Rats, Hairless; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption
chemical_list: D058891:5-alpha Reductase Inhibitors; D018120:Finasteride
keywords: finasteride; formulation vehicles; hydroxypropyl chitosan; in vitro models; in vitro/in vivo correlations; penetration; permeation; pharmacokinetics; skin