title: Intradermal concentration of hydroquinone after application of hydroquinone ointments is higher than its cytotoxic concentration.
abstract: Ointments of the skin depigmentation agent hydroquinone (HQ) have been prepared by extemporaneous nonsterile compounding in our hospital. The HQ ointments were highly effective in the treatment of various types of skin pigmentations; however, various problems have emerged including chromatic aberration of the ointments, a relatively large variability of efficacy, and mild topical side effects including irritation. In this paper, the cytotoxicity of HQ was assessed in vitro using rat skin fibroblasts as the concentration with 50% survival after 24 h exposure to be 16.5 microM. The intradermal concentrations at 2 h after application of the HQ ointments was also estimated to be 358 mM and 51.7 mM in stratum corneum and viable tissue (viable epidermis+dermis), respectively, by an in vitro rat skin permeation study with rat full-thickness abdominal skin and Franz-type diffusion cells. It was demonstrated that the intradermal concentration of HQ was much higher than that eliciting cytotoxicity, suggesting that the topical side effects after application of HQ ointment were due to the cytotoxicity of HQ.
authors.affiliation: Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan.
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Matsubayashi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaeda
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kita
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Kurimoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kohshi
authors.initials: K
authors.lastname: Nishiguchi
authors.forename: Takuya
authors.initials: T
authors.lastname: Fujita
authors.forename: Fumio
authors.initials: F
authors.lastname: Kamiyama
authors.forename: Akira
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003124:Colorimetry; D004058:Diffusion; D005347:Fibroblasts; D006873:Hydroquinones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D008297:Male; D009824:Ointments; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D012869:Skin Absorption; D013431:Sulfates / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D006873:Hydroquinones; D009824:Ointments; D013431:Sulfates; C012036:sodium sulfate; D001205:Ascorbic Acid; C031927:hydroquinone