In vivo time-course of receptor binding in the parathyroid gland of the vitamin D analogue [3H]1,25-dihydroxy-22-oxavitamin D3 compared with [3H]1,25-dihydroxyvitamin D3, determined by micro-autoradiography

Abstract

1,25-Dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT), is a new synthetic analogue of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol), to be used in the treatment of secondary hyperparathyroidism. This study used receptor micro-autoradiography in the parathyroid gland to determine and compare the time-course of receptor binding between OCT and 1,25(OH)(2)D(3). Mice were injected with 4 microg/kg of [26-(3)H]OCT or [26,27-methyl-(3)H]1,25(OH)(2)D(3), and killed at 5, 15, 30 min, 1, 2, 4, 8, 12, and 24 h afterwards. Thyroid-parathyroid tissue was excised and autoradiograms were prepared. Under identical conditions of dose and adjusted specific radioactivity between [(3)H]OCT and [(3)H]1,25(OH)(2)D(3), the plasma concentration of [(3)H]OCT was much lower than that of [(3)H]1,25(OH)(2)D(3). In the parathyroid at all time points, chief cell nuclei were labelled with varying degrees while connective tissue cells remained unlabelled. Nuclear receptor binding of [(3)H]OCT appeared equal to or higher than that of [(3)H]1,25(OH)(2)D(3). Nuclear uptake of [(3)H]OCT was maximal at 15 min and higher than that of [(3)H]1,25(OH)(2)D(3), which was maximal at 1 h after injection. Low levels of nuclear retention of the two compounds were still similarly detectable at 12 h. The results indicate the high affinity of OCT to parathyroid cells, and suggest that OCT has a higher therapeutic potential than 1,25(OH)(2)D(3), especially under clinical conditions, at which OCT with its lower calcaemic effect would allow treatment with a dose several times higher than 1,25(OH)(2)D(3).

Surgical Treatment of Secondary Hyperparathyroidism due to Chronic Kidney Disease

“…maxacalcitol or falecalcitriol, which are available in Japan, and 1-alpha-OH-D2 and 19Nor-1,25(OH)2 D2 (Zemplar) can be used (27)(28)(29)(30)(31)(32). However, hypercalcaemia and hyperphosphataemia are readily induced by these medicines and sometimes 2HPT is resistant to these drugs.…”

Clinical Features and Hyperplastic Patterns of Parathyroid Glands in Hemodialysis Patients With Advanced Secondary Hyperparathyroidism Refractory to Maxacalcitol Treatment and Required Parathyroidectomy

“…One such analog is 22‐oxa calcitriol (Maxacalcitol, OCT), a drug developed by Chugai Pharmaceutical Company in Japan (3–5). In a uremic rat model, OCT was able to suppress PTH in a less calcemic manner than calcitriol because OCT has less affinity for vitamin D binding protein and VDR, which shorten the half‐life (4,5). The effectiveness of OCT has been confirmed in HD patients with moderate to severe 2HPT (6–8).…”

Is the Volume of the Parathyroid Gland a Predictor of Maxacalcitol Response in Advanced Secondary Hyperparathyroidism?

“…22‐oxa calcitriol (Maxacalcitol, OCT; Chugai Pharmaceutical, Tokyo, Japan) is one of these analogs to be developed by the Chugai pharmaceutical company in Japan (3). In a uremic rat model, OCT can reduce the PTH level in a less calcemic manner than calcitriol because OCT has reduced affinity for vitamin D binding protein and VDR which induce a short half‐life (4,5). The effectiveness of OCT has been confirmed in hemodialysis patients with moderate or severe 2HPT (6,7).…”