In vivo assessment of the cutaneous bioavailability of topically applied maxacalcitol

Abstract

Maxacalcitol (22-oxacalcitriol), a vitamin D3 analogue, is widely used for the treatment of psoriasis. The effects of topical dermatologic drugs have been assessed by their pharmacodynamic activities, and concentrations in the skin correlate with these activities. In this study, we assessed the cutaneous bioavailability of topically applied maxacalcitol ointment in vivo by tape stripping. Six drug application sites were randomly assigned on the left volar forearm of six healthy men. Fifty milligrams of maxacalcitol ointment (25 microg/g) was applied to each site. After 0 (15 s), 0.5, 1, 2, 4, or 6 h, the ointment was gently removed, and tape stripping was performed. Maxacalcitol was extracted from the tape strips and quantified by liquid chromatographic tandem mass spectrometry. Average concentrations of maxacalcitol in the stratum corneum (SC) were 2.61, 4.37, 6.23, 9.37, and 9.46 microg/g at 0.5, 1, 2, 4, and 6 h, respectively, after drug application. The steady state was attained approx. 4 h after drug application. The cutaneous bioavailability of topical maxacalcitol ointment can be assessed by the tape-stripping method. This approach will probably be useful in the assessment of the bioequivalence of topical dermatologic products and as a parameter for pharmacokinetic/pharmacodynamic studies.