Cutaneous pharmacokinetics of topically applied maxacalcitol ointment and lotion.
Maxacalcitol (22-oxacalcitriol), a vitamin D3 analogue, is widely used for the treatment of psoriasis in Japan. The effects of topically applied dermatologic preparations have routinely been assessed by their pharmacodynamic profiles and their concentrations in the skin correlate well with these profiles.


OBJECTIVE
Recently, a maxacalcitol lotion formulation (M514102) was developed for the treatment of psoriatic lesions on the face and scalp. To predict the clinical efficacy of the lotion, we investigated the cutaneous bioavailability of topically applied lotion and compared this with that of its ointment formulation in healthy subjects.


METHODS
In the first study, 12 subjects were divided into two groups of 6 each and were treated with the ointment or lotion. Six drug application sites were randomly selected on the left volar forearm. After 0, 2, 4, 6, 8 and 10 h, the formulations were gently removed and tape stripping was performed. Maxacalcitol was extracted from the tape strips and quantified by liquid chromatographic tandem mass spectrometry. In the second study, four drug application sites were randomly selected on the left volar forearm in the 12 subjects. The ointment was applied and spread over two sites and the lotion was applied in the same manner over the remaining two sites. After 8 h, the preparations were gently removed and followed by tape stripping.


RESULTS
The average concentrations of maxacalcitol in the stratum corneum (SC) at 2, 4, 6, 8 and 10 h after application were 6.9 +/- 3.3, 12.8 +/- 6.2, 11.8 +/- 4.6, 13.1 +/- 5.2 and 12.3 +/- 3.1 microg/g for the ointment and 3.1 +/- 1.0, 9.1 +/- 3.1, 13.9 +/- 3.4, 13.1 +/- 4.1 and 15.5 +/- 3.1 microg/g for the lotion, respectively. A steady state was observed at approximately 4 and 6 h after application of the ointment and lotion, respectively. In the second study, there was no significant difference between the average of the SC concentrations of the ointment and lotion at 8 h.


CONCLUSIONS
In conclusion, we observed that assessment of cutaneous bioavailability by using tape stripping was reproducible. Accordingly, the cutaneous bioavailability of the lotion was comparable to that of its ointment. Hence, treatment with the lotion is expected to be as effective as that with the ointment.
Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan. umemura@hama-med.ac.jp
K
K
Umemura
Y
Y
Ikeda
K
K
Kondo
K
K
Hirata
H
H
Amagishi
Y
Y
Ishihama
Y
Y
Tokura
D000279:Administration, Cutaneous; D000328:Adult; D001682:Biological Availability; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004304:Dosage Forms; D006801:Humans; D008297:Male; D009824:Ointments; D015203:Reproducibility of Results; D012869:Skin Absorption; D053719:Tandem Mass Spectrometry; D013997:Time Factors
D003879:Dermatologic Agents; D004304:Dosage Forms; D009824:Ointments; D002117:Calcitriol; C051883:maxacalcitol