Pharmacokinetics of intra-articular vitamin D analogue calcipotriol in sheep and metabolism in human synovial and mesenchymal stromal cells

Publication date: Available online 15 December 2018Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Jere Huovinen, Maija Haj Hussain, Markus Niemelä, Sakari Laaksonen, Hanna-Marja Voipio, Juha Jyrkäs, Janne Mannila, Toni Lassila, Ari Tolonen, Sanna Turunen, Ulrich Bergmann, Petri Lehenkari, Johanna A. HuhtakangasAbstractCalcipotriol (MC903) is a side chain analogue of the biologically active 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Due to its anti-inflammatory and anti-proliferative effects on stromal cells, calcipotriol is a promising candidate for the local treatment of arthritis. In this preliminary work, we studied the pharmacokinetics and safety of calcipotriol after an IV (0.1 mg/kg given to one sheep) and intra-articular dose (0.054 mg/kg, 0.216 mg/kg and 0.560 mg/kg given to three sheep). The terminal half-life of calcipotriol was approximately 1 hour after an IV dose. After intra-articular dosing, the systemic absorption was between 1 and 13% during the observed 24 hours. Hypercalcemia or other clinical adverse effects did not occur in any animal during the study, and no macroscopic or microscopic alterations were seen in the synovium of the calcipotriol-injected knees compared to the vehicle knees. The in vitro metabolism of calcipotriol was analyzed with LC-MS from human synovial and mesenchymal stromal cell cultures. Both cell types were able to metabolize calcipotriol with MC1080 and MC1046 as the main metabolites. CYP24 ...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research