Toxicokinetics and clinical kinetics of topically applied vitamin D analogues

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Abstract
The effects of calcitriol and calcipotriol ointments on calcium homeostasis in rats were investigated. Three groups of five rats received 4 daily applications of either calcitriol ointment (3 μg/g), calcipotriol ointment (50 μg/g) or vehicle on the back (area 75 cm2). Blood and urine were collected during treatment and for 7 days after the last dose. Calcitriol ointment did not affect any of the parameters studied. Calcipotriol ointment caused a significant increase in urinary calcium and phosphate excretion and severe downregulation of endogenous calcitriol levels occurred, up to 7 days after the last dose. Calcipotriol could still be detected in the last plasma sample. In order to substantiate the safety of calcitriol ointment in clinical practice, plasma calcitriol levels were determined in clinical trial patients. Over 2000 samples from more than 400 patients with chronic plaque psoriasis were analysed. There was no indication of increased plasma calcitriol when patients were treated with calcitriol ointment (3 μg/g twice daily) for up to 78 weeks at body surface areas up to 6000 cm2. At higher body surface areas insufficient data were available. It is concluded that calcitriol ointment does not affect calcium homeostasis in rats, whereas calcipotriol ointment has a prolonged effect on it. Plasma calcitriol levels in clinical trials indicate that calcitriol ointment is a safe treatment for chronic plaque psoriasis.