Cutaneous pharmacokinetics of topically applied maxacalcitol ointment and lotion.

UNLABELLED: 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. OBJECTIVES: 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.

Absorption of phenol red and bromphenol blue as model drugs from the peritoneal cavity around the liver surface in rats.

The importance of the injection site on the pharmacokinetics of phenol red and bromphenol blue as model drugs after intraperitoneal administration into rat was examined. Their absorption rate from the peritoneal cavity was faster after intraperitoneal administration to the liver surface than that after intraperitoneal administration to the distal small intestine, as shown by the increase in maximum concentration and decrease in mean residence time in plasma. A similar tendency was observed in the biliary excretion pattern. The enhanced absorption rate was supported by the significantly smaller amount of both drugs remaining in the peritoneal cavity at 15 min after liver surface administration than that after small intestine administration. The liver concentration of the model drugs at 15 min after liver surface administration was 1.5-2.0 times that after small intestine administration. Accordingly, liver surface administration was shown to be effective with good absorption and efficient drug delivery to the liver.