Pharmacokinetic disposition of topical phosphodiesterase-4 inhibitor E6005 in patients with atopic dermatitis

Yasumi Kitahara, Seiichiro Hojo, Maiko Nomoto, Daisuke Onozuka, Masutaka Furue, Akihito Hagihara

Research output: Contribution to journalArticlepeer-review


BACKGROUND: A novel topical phosphodiesterase-4 inhibitor E6005 shows potential as effective treatment options for atopic dermatitis (AD); however, systemic exposure may cause potentially undesirable adverse reactions. In this study, we evaluated the relationship between the systemic exposure of E6005 and clinical parameters including skin condition and the incidence of AEs in patients with AD.

METHODS: The association analysis used the clinical data obtained in a previously conducted clinical study with topical E6005 in adult patients with AD. To estimate associations with drug exposure, generalized estimating equation logistic regression models were used, along with clinical data and plasma concentrations of M11, major metabolite of E6005 (as an indicator for E6005 exposure).

RESULTS: The metabolite M11 was detected in 62 of 221 plasma samples from 72 subjects. From association analysis, SCORAD-A obtained prior to E6005 treatment was identified as the clinical parameter influenced to M11 detection with statistical significance (p = 0.003). M11 detection was not clearly associated with the incidence of adverse events occurred.

CONCLUSION: Exposure to topical E6005 is associated with the eczema-associated area, however, that is not distinctly associated with its adverse drug reactions occurred after drug applications possibly due to E6005's characteristics of tissue distribution.

Original languageEnglish
Pages (from-to)1-23
Number of pages23
JournalJournal of Dermatological Treatment
Publication statusE-pub ahead of print - Sept 28 2018


Dive into the research topics of 'Pharmacokinetic disposition of topical phosphodiesterase-4 inhibitor E6005 in patients with atopic dermatitis'. Together they form a unique fingerprint.

Cite this