Toxicokinetics of topically applied calcitriol and calcipotriol in rats

Two topically applied vitamin D analogs were investigated for their effects on calcium homeostasis in the rat. Calcitriol ointment (3 micrograms/g), calcipotriol ointment (50 micrograms/g), or vehicle were applied daily for 4 days on the shaven back of the rats (n = 5 per group) over an area of 75 cm2. Blood and urine samples were collected before and during treatment and for 7 days after the last dose. Application of calcipotriol ointment resulted in a significant increase in urinary calcium and phosphate excretion and severe down-regulation of endogenous calcitriol levels, up to 7 days after the last dose. Calcipotriol could still be detected in the last plasma sample. In contrast, calcitriol ointment had no significant effects relative to vehicle on any of the parameters studied. Calcitriol ointment (3 micrograms/g) does not appear to affect calcium homeostasis in rats, whereas calcipotriol ointment has a prolonged effect.