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Target site pharmacokinetics of doxycycline for rosacea in healthy volunteers is independent of food-effect (PI Markus Zeitlinger).

Br J Clin Pharmacol. 2018 Jul 22;:

Authors: Pal A, Matzneller P, Gautam A, Österreicher Z, Wulkersdorfer B, Reiter B, Stimpfl T, Zeitlinger M

Abstract
AIMS: DFD-09 (doxycycline) oral capsules 40 mg are approved for the treatment of inflammatory lesions of rosacea. Unlike the food-induced lowering of doxycycline's peak plasma concentration (Cmax ), its exposure under fed conditions in skin, the drug's target site for rosacea, is unknown. The present study explored the effect of food on dermal pharmacokinetics of doxycycline.
METHODS: Pharmacokinetics of doxycycline in dermal interstitial fluid (d-ISF) and plasma of healthy volunteers were assessed in parallel groups under fed (n=6) and fasting (n=6) conditions during a 14-day once-daily treatment course with Doxycycline oral capsules 40 mg (DFD-09). Sampling of d-ISF and plasma were performed on days 1, 10 (fasting group d-ISF only) and 14.
RESULTS: Twelve subjects were randomised, 11 analysed. No causally drug-related adverse events occurred. Dermal doxycycline exposures (Cmax and AUC) under fed state were about 30% lower than fasting state at day 1 but were similar at steady-state. In analogy to skin, plasma exposure showed no between-group difference at steady-state. Accumulation ratios were higher in skin than in plasma. Correcting for plasma protein binding (~90%), dermal doxycycline exposure was approximately 3-fold higher than unbound plasma exposure.
CONCLUSIONS: At steady state, doxycycline concentrations in skin of fed and fasting healthy volunteers were comparable. Doxycycline's efficacy in rosacea is possibly due to considerable dermal accumulation of unbound doxycycline and is independent of food-effect. EudraCT registration number 2016-001622-34.

PMID: 30033542 [PubMed - as supplied by publisher]

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