PubMed Health⌕ Search

Biomedical subjects

Noboru Kubodera

Publications and source records attributed to Noboru Kubodera.

17 recordsLinked to original sources
PubMed2007

Synthesis and biological evaluation of a 3-positon epimer of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71).

1alpha,25-Dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (ED-71), an analog of active vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], possesses a hydroxypropoxy substituent at the 2beta-position of 1,25(OH)(2)D(3). ED-71 has potent biological effects on bone and is currently under phase III clinical studies for bone fracture prevention. It is well-known that the synthesis and secretion of parathyroid hormone (PTH) is regulated by 1,25(OH)(2)D(3). Interestingly, during clinical development of ED-71, serum intact PTH in osteoporotic patients did not change significantly upon treatment with ED-71. The reason remains unclear, however. Brown et al. reported that 3-epi-1,25(OH)(2)D(3), an epimer of 1,25(OH)(2)D(3) at the 3-position, shows equipotent and prolonged activity compared to 1,25(OH)(2)D(3) at suppressing PTH secretion. Since ED-71 has a bulky hydroxypropoxy substituent at the 2-position, epimerization at the adjacent and sterically hindered 3-position might be prevented, which may account for its weak potency in PTH suppression observed in clinical studies. We have significant interest in ED-71 epimerization at the 3-position and the biological potency of 3-epi-ED-71 in suppressing PTH secretion. In the present studies, synthesis of 3-epi-ED-71 and investigations of in vitro suppression of PTH using bovine parathyroid cells are described. The inhibitory potency of vitamin D(3) analogs were found to be 1,25(OH)(2)D(3)>ED-71> or =3-epi-1,25(OH)(2)D(3)>>3-epi-ED-71. ED-71 and 3-epi-ED-71 showed weak activity towards PTH suppression in our assays.

Animals↗
PubMed2006

Synthesis and evaluation of a 3-position diastereomer of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71).

A 3-position diastereomer of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71, 2), 3-epi-ED-71 (4), was synthesized by the convergent method coupling the A-ring fragment (5) with the C/D-ring fragment (6). As the results of preliminary in vitro biological evaluation of 3-epi-ED-71 (4), the inhibition of parathyroid hormone secretion in bovine parathyroid cells and binding affinity to human recombinant vitamin D receptor and to human vitamin D binding protein in comparison with ED-71 (2), 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3, 1), and 3-epi-1,25(OH)2D3 (3) are described.

Animals↗
PubMed2006

Synthesis of putative metabolites of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (ED-71).

1alpha,25-Dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (ED-71), an analog of active vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] is under phase III clinical trials in Japan for the treatment of osteoporosis and bone fracture prevention. Since ED-71 has a substituent at the 2beta-position of the A-ring, it is recognized that the metabolic pathway of ED-71 might be more complicated than 1,25(OH)(2)D(3) because of metabolism at the 2beta-position substituent in addition to the inherent metabolism of the side chain. To clarify the metabolism of hydroxypropoxy substituent of the 2beta-positon and a combination of metabolism between side chain and 2beta-positon, four putative metabolites of ED-71 have been prepared as authentic samples. The metabolites at the 2beta-positon, the methyl ester derivative considered as an ester standard of the oxidized metabolite and the tetraol derivative as the truncated metabolite were synthesized from alpha-epoxide, a key intermediate of ED-71 synthesis. The combination metabolites between side chain and 2beta-positon, the 24(S)- and 24(R)-pentaols were synthesized using Trost's convergent method.

Bone Density Conservation Agents↗
PubMed2006

[Progress in research on vitamin D analogs].

A little over two decades ago, the vitamin D activation pathway was elucidated and alfacalcidol arrived on the scene as a prodrug for active vitamin D, 1,25-dihydroxyvitamin D(3), to remedy vitamin D deficiency. With the concurrent reported discovery of the differentiation-inducing effect of active vitamin D, its diverse physiological effects have become appreciated and the research aiming to accentuate selected physiological effects by analog research has made a fresh development. Our studies aimed particularly at separating the differentiation-inducing effect/cell growth-inhibitory effect and the calcemic effect of active vitamin D led to the development of two characteristic analogs, OCT and ED-71. OCT, characterized by its profound differentiation-inducing effect and modest calcemic effect, is currently in practical use as an injectable therapeutic agent for secondary hyperparathyroidism as well as in clinical settings as an ointment for the treatment of psoriasis vulgaris. The other analog, ED-71, possesses a profile inverse to that of OCT and is now under clinical development as an oral preparation for treatment of osteoporosis. The present overview refers to methodology of searching next-generation analogs, exemplifying a new analog, DD-281, based on the knowledge accumulated through development of OCT and ED-71.

Animals↗
PubMed2005

Measurement and characterization of C-3 epimerization activity toward vitamin D3.

Recently, epimerization of the hydroxyl group at C-3 has been identified as a unique metabolic pathway of vitamin D compounds. We measured C-3 epimerization activity in subcellular fractions prepared from cultured cells and investigated the basic properties of the enzyme responsible for the epimerization. C-3 epimerization activity was detected using a NADPH-generating system containing glucose-6-phosphate, NADP, glucose-6-phosphate dehydrogenase, and Mg(2+). The highest level of activity was observed in a microsomal fraction prepared from rat osteoblastic UMR-106 cells but activity was also observed in microsomal fractions prepared from MG-63, Caco-2, Hep G2, and HUH-7 cells. In terms of maximum velocity (V(max)) and the Michaelis constant (K(m)), 25-hydroxyvitamin D(3) [25(OH)D(3)] exhibited the highest specificity for the epimerization at C-3 among 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], 25(OH)D(3), 24,25-dihydroxyvitamin D(3) [24,25(OH)(2)D(3)], and 22-oxacalcitriol (OCT). The epimerization activity was not inhibited by various cytochrome P450 inhibitors and antiserum against NADPH cytochrome P450 reductase. Neither CYP24, CYP27A1, CYP27B1 nor 3(alpha-->beta)hydroxysteroid epimerase (HSE) catalyzed the epimerization in vitro. Based on these results, the enzyme(s) responsible for the epimerization of vitamin D(3) at C-3 are thought to be located in microsomes and different from cytochrome P450 and HSE.

Animals↗
PubMed2005

22-Oxa-1alpha,25-dihydroxyvitamin D3 inhibits metastasis and angiogenesis in lung cancer.

1alpha,25-Dihydroxyvitamin D(3) (1alpha,25-D(3)) has potent antiproliferative and anti-invasive properties in vitro in cancer cells. However, its calcemic effect in vivo limits its therapeutic applications. Here, we report the efficacy of 22-oxa-1alpha,25-dihydroxyvitamin D(3) (22-oxa-1alpha,25-D(3)), a low calcemic analog of vitamin D, against the development of metastatic lung carcinoma after an intravenous injection of green fluorescent protein-transfected Lewis lung carcinoma (LLC-GFP) cells in C57BL/6 mice. The mice injected with tumor cells were implanted simultaneously with osmotic minipumps containing either 1alpha,25-D(3), 22-oxa-1alpha,25-D(3) or vehicle. The 1alpha,25-D(3) treatment group had been hypercalcemic, but the 22-oxa-1alpha,25-D(3) and vehicle treatment groups remained normocalcemic for the duration of the experiment. The total number of lung metastases, lung weight and the expression of GFP mRNA in the lung were markedly decreased in 1alpha,25-D(3) and 22-oxa-1alpha,25-D(3)-treated mice. In the in vitro experiment, 1alpha,25-D(3) and 22-oxa-1alpha,25-D(3) reduced the expression of matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor and parathyroid hormone-related protein in LLC-GFP cells. Furthermore, in the angiogenesis assay, the number of tumor cells or basic fibroblast growth factor-induced angiogenesis was reduced in 1alpha,25-D(3) and 22-oxa-1alpha,25-D(3)-treated mice. Moreover, using a new experimental model of vitamin D receptor (VDR) null mutant (VDR(-/-)) mice with corrected hypocalcemia and hypervitaminosis D, we examine the anti-cancer effect of 22-oxa-1alpha,25-D(3) without other functions induced by 22-oxa-1alpha,25-D(3) in the host. In the VDR(-/-) mice, 22-oxa-1alpha,25-D(3) directly inhibited the metastatic activity of LLC-GFP cells in a dose-dependent manner without exerting a direct influence on the calcemic activity or other actions regulated by 22-oxa-1alpha,25-D(3) in the host. These results indicate that the inhibition of metastasis and angiogenesis-inducing activity in cancer cells seemed to be a major mechanism responsible for the anti-cancer effects of 22-oxa-1alpha,25-D(3). Our findings show that 22-oxa-1alpha,25-D(3) is beneficial for the prevention of metastasis in lung carcinoma.

Angiogenesis Inhibitors↗
PubMed2005

[Vitamin D and bone quality].

Active vitamin D analogs such as alfacalcidol have been shown to reduce fracture risk in clinical trials in spite of its moderate effects on bone mass. It has been reported that active vitamin D analogs may improve bone quality, by amelioration of bone microarchitecture, by specific effect on cortical bones, by acceleration of calcification, and by effect on nature of bone matrix proteins. The bone quality assessments that clarify the effect on bone mechanical properties will become important for the positioning of osteoporosis drugs.

Animals↗
PubMed2004

C-3 epimerization of vitamin D3 metabolites and further metabolism of C-3 epimers: 25-hydroxyvitamin D3 is metabolized to 3-epi-25-hydroxyvitamin D3 and subsequently metabolized through C-1alpha or C-24 hydroxylation.

Recently, it was revealed that 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) and 24R,25-dihydroxyvitamin D3 (24,25(OH)2D3) were metabolized to their respective epimers of the hydroxyl group at C-3 of the A-ring. We now report the isolation and structural assignment of 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3 as a major metabolite of 25-hydroxyvitamin D3 (25(OH)D3) and the further metabolism of C-3 epimers of vitamin D3 metabolites. When 25(OH)D3 was incubated with various cultured cells including osteosarcoma, colon adenocarcinoma, and hepatoblastoma cell lines, 3-epi-25(OH)D3 and 24,25 (OH)2D3 were commonly observed as a major and minor metabolite of 25(OH)D3, respectively. 25(OH)D3 was at least as sensitive to C-3 epimerization as 1alpha, 25(OH)2D3 which has been reported as a substrate for the C-3 epimerization reaction. Unlike these cultured cells, LLC-PK1 cells, a porcine kidney cell line, preferentially produced 24,25(OH)2D3 rather than 3-epi-25(OH)D3. We also confirmed the existence of 3-epi-25(OH)D3 in the serum of rats intravenously given pharmacological doses of 25(OH)D3. The cultured cells metabolized 3-epi-25OHD3 and 3-epi-1alpha,25(OH)2D3 to 3-epi-24,25(OH)2D3 and 3-epi-1alpha,24,25(OH)3D3, respectively. In addition, we demonstrated that 3-epi-25(OH)D3 was metabolized to 3-epi-1alpha,25(OH)2D3 by CYP27B1 and to 3-epi-24,25(OH)2D3 by CYP24 using recombinant Escherichia coli cell systems. 3-Epi-25(OH)D3, 3-epi-1alpha,25(OH)2D3, and 3-epi-24,25(OH)2D3 were biologically less active than 25(OH)D3, 1alpha,25(OH)2D3, and 24,25(OH)2D3, but 3-epi-1alpha,25(OH)2D3 showed to some extent transcriptional activity toward target genes and anti-proliferative/differentiation-inducing activity against human myeloid leukemia cells (HL-60). These results indicate that C-3 epimerization may be a common metabolic pathway for the major metabolites of vitamin D3.

24,25-Dihydroxyvitamin D 3↗
PubMed2004

Cell specificity and properties of the C-3 epimerization of Vitamin D3 metabolites.

It is well documented that Vitamin D3 metabolites and synthetic analogs are metabolized to their epimers of the hydroxyl group at C-3 of the A-ring. We investigated the C-3 epimerization of Vitamin D3 metabolites in various cultured cells and basic properties of the enzyme responsible for the C-3 epimerization. 1alpha,25-Dihydroxyvitamin D3 [1alpha,25(OH)2D3], 25-hydroxyvitamin D3 [25(OH)D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were metabolized to the respective C-3 epimers in UMR-106 (rat osteosarcoma), MG-63 (human osteosarcoma), Caco-2 (human colon adenocarcinoma), LLC-PK1 (porcine kidney) and HepG2 (human hepatoblastoma)] cells, although the differences existed in the amount of each C-3 epimer formed with different cell types. In terms of maximum velocity (Vmax) and Michaelis constant (Km) values for the C-3 epimerization in microsome fraction of UMR-106 cells, 25(OH)D3 exhibited the highest specificity for the C-3 epimerization among 1alpha,25(OH)2D3, 25(OH)D3 and 24,25(OH)2D3. C-3 epimerization activity was not inhibited by various cytochrome P450 inhibitors and antiserum against NADPH cytochrome P450 reductase. Neither CYP24, CYP27A1, CYP27B1 nor 3(alpha --> beta) -hydroxysteroid epimerase (HSE) catalyzed the C-3 epimerization in vitro. Based on these results, the enzyme responsible for the C-3 epimerization of Vitamin D3 are thought to be different from already-known cytochrome P450-related Vitamin D metabolic enzymes and HSE.

Animals↗
PubMed2004

Management of calcium and bone abnormalities in hemodialysis patients.

In chronic renal failure, hyperphosphatemia, hypocalcemia, hyperparathyroidism, reduced activation of vitamin D, decreased level of calcium-sensing receptor, osteitis fibrosa, and osteomalacia are features related to calcium abnormalities. Hyperparathyroidism is a risk factor for survival of hemodialysis patients as well as hypoparathyroidism, which is another feature in hemodialysis patients. Treatment of these abnormalities includes control of parathyroid hormone (PTH) secretion, counteracting hyperphosphatemia, correction of hypocalcemia, and others. Various kinds of vitamin D analogs have been introduced recently in addition to calcitriol and alfacalcidol, which have a rather long history (eg, maxacalcitol and falecalcitriol). Sevelamer is a newly developed phosphate binder to treat soft-tissue calcification.

Bone Diseases↗
PubMed2002

Two novel metabolic pathways of 22-oxacalcitriol (OCT). C-25 dehydration and C-3 epimerization and biological activities of novel OCT metabolites.

22-Oxacalcitriol (OCT) is an analog of calcitriol, characterized by potent differentiation-inducing activity and low calcemic liability. The metabolism of OCT has been studied and its polar metabolites, such as 24/26-hydroxylated-OCT and hexanor-1 alpha,20-dihydroxyvitamin D(3) (1 alpha,20(OH)(2)D(3)), have been identified. In contrast, little is known about the less polar metabolites of OCT, which have been found in relatively large amounts. In this study, the in vitro metabolism of OCT was studied in UMR 106, Caco-2, and LLC-PK(1) cells to identify the less polar metabolites and to assess their biological activity. OCT was initially metabolized to three less polar metabolites, 3-epi-OCT and two dehydrates, 25-dehydroxy- 25-ene-22-oxa-1 alpha(OH)D(3) (25-ene-22-oxa-1 alpha(OH)D(3)) and 25-dehydroxy-24-ene-22-oxa-1 alpha(OH)D(3) (24-ene-22-oxa-1 alpha(OH)D(3)). We also observed further metabolites, the two C-3 epimers of the C-25 dehydrates, 25-ene-3-epi-22-oxa-1 alpha(OH)D(3) and 24-ene-3-epi-22-oxa-1 alpha(OH)D(3). The structures of these metabolites were successfully assigned by (1)H NMR and LC-MS analyses. The three cell lines differ in their ability to metabolize OCT through the C-3 epimerization or the C-25 dehydration pathway. The biological activity of the OCT metabolites assessed by a luciferase reporter gene transcriptional activation system, binding assays for the vitamin D receptor (VDR) and vitamin D-binding protein (DBP), and assays for regulatory activities of cell differentiation and proliferation was found to be lower than that of OCT. Thus, both the C-3 epimerization and C-25 dehydration may work to reduce the biological activity of OCT.

Animals↗
PubMed2002

A comparison between daily and thrice-weekly i.v. administration of 1,25-dihydroxy-22-oxavitamin D(3) regarding suppression of parathyroid hormone secretion and calcaemic action in uraemic rats.

BACKGROUND: 1,25-Dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) is an analogue of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol) with less calcaemic activity, thus more suitable than 1,25(OH)(2)D(3) for the control of parathyroid hormone (PTH) secretion in chronic dialysis patients. As the low-calcaemic action of OCT has been mainly attributed to its short half-life in the blood stream, the number of doses per week is the key factor to effective OCT therapy toward suppression of PTH secretion and hypercalcaemia. Thus, we investigated a comparison between daily and thrice-weekly i.v. administration of OCT regarding suppression of PTH secretion and calcaemic action in 5/6 nephrectomized rats as a model for chronic renal failure. METHODS: Model rats of chronic renal failure were made by 5/6 nephrectomy. At 3 months after surgery, they were administered either vehicle or OCT intravenously, daily (0.125 or 0.625 microg/kg) or thrice-weekly (0.6 or 3.0 microg/kg) for 2 weeks. RESULTS: The data show that 0.625 microg/kg/day (=4.375 microg/kg/week) suppresses PTH secretion with significant increase in calcium levels at 24 h after the final administration, on the other hand, 3.0 microg/kg/ thrice-weekly (=9.0 microg/kg/week) suppresses PTH secretion, although moderate compared with 0.625 microg/kg/day, with a slight (not significant) increase in calcium. CONCLUSIONS: The current clinical mode of OCT therapy, i.v. thrice-weekly administration, is a practically recommendable protocol.

Animals↗
PubMed2002

A comparison between 1,25-dihydroxy-22-oxavitamin D(3) and 1,25-dihydroxyvitamin D(3) regarding suppression of parathyroid hormone secretion and calcaemic action.

BACKGROUND: Since Slatopolsky et al. (J Clin Invest 1984; 74: 2136-2143) reported the effect of active vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), on secondary hyperparathyroidism (2HPT) which accompanies chronic renal failure, there have been several studies of the therapeutic effects of 1,25(OH)(2)D(3) in this disease. Although parathyroid hormone (PTH) is suppressed by treatment with 1,25(OH)(2)D(3), long-term treatment with 1,25(OH)(2)D(3) tends to induce hypercalcaemia. Therefore, an analogue of 1,25(OH)(2)D(3), 1,25-dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) with less calcaemic activity, was developed for the treatment of 2HPT. METHODS: In order to clarify the differences between the effects of 1,25(OH)(2)D(3) and OCT on 2HPT associated with chronic renal failure, these compounds were administered by intermittent i.v. injection for 2 weeks in rats with mild to moderate uraemia. RESULTS: 1,25(OH)(2)D(3) markedly suppressed PTH levels, but increased serum calcium (Ca). OCT also markedly suppressed PTH levels, but induced only a slight increase in serum Ca. 1,25(OH)(2)D(3) caused a dose-dependent decrease in body weight, whereas OCT had no effect on body weight in uraemic rats. Based on those doses of OCT and 1,25(OH)(2)D(3), which resulted in a 60% suppression of PTH, and induced hypercalcaemia, we consider the relative ratios for efficacy and Ca-elevating activity between OCT and 1,25(OH)(2)D(3) to be 1 : 8 and 1 : 48, respectively. CONCLUSIONS: OCT suppressed PTH levels with a slight increase in serum Ca without changing the body weight in uraemic rats. This observation suggests that OCT might be a useful vitamin D analogue for 2HPT management in long-term clinical treatment.

Animals↗
PubMed2002

Effects of i.v. and oral 1,25-dihydroxy-22-oxavitamin D(3) on secondary hyperparathyroidism in dogs with chronic renal failure.

BACKGROUND: 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol) has been used for the treatment of secondary hyperparathyroidism (2HPT) associated with chronic renal failure (CRF). However, hypercalcaemia frequently precludes the administration of ideal doses of 1,25(OH)(2)D(3). 1,25-Dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) is an analogue of 1,25(OH)(2)D(3) with less calcaemic activity. Several investigators have reported the effect of this analogue on suppressing parathyroid hormone (PTH) in vitro and in vivo in rats and dogs. METHODS AND RESULTS: The first experiments were designed to compare the relative potency of an i.v. injection of OCT and 1,25(OH)(2)D(3) (i.v. OCT vs i.v. 1,25(OH)(2)D(3)) on serum PTH and ionized calcium (ICa). A single dose of OCT (5 microg/kg) to uraemic dogs suppressed PTH by 81% without a statistical significant change in serum ICa. On the other hand, any of the effective doses of 1,25(OH)(2)D(3) on PTH suppression were hypercalcaemic. The intermittent administration of OCT (0.1 microg/kg) or 1,25(OH)(2)D(3) (0.025 microg/kg), three times per week i.v. suppressed serum PTH by 89 or 77%, respectively without hypercalcaemia. To evaluate OCT as an oral drug, it was given intermittently (three times per week) to a group of six dogs for a period of 4 weeks. Subsequently, it was changed to a daily administration (0.05 microg/kg) for a period of 2 weeks. Finally the dose was reduced to 0.025 microg/kg. Daily OCT 0.05 microg/kg suppressed serum PTH by 67%. Subsequently, 0.025 microg/kg maintained serum PTH within the normal range without hypercalcaemia for 4 weeks. The time course of serum OCT concentrations following a single i.v. or oral OCT dose to uraemic dogs showed that oral OCT was rapidly absorbed and reached maximum plasma concentration and its disappearance from blood was similar to that of i.v. injection. CONCLUSIONS: In conclusion, our results suggest that OCT is a useful vitamin D(3) analogue, with a potentially larger therapeutic window than that of i.v. 1,25(OH)(2)D(3) and which is available for i.v./oral, in the management of 2HPT.

Administration, Oral↗
PubMed2002

[Use and indication of vitamin D and vitamin D analogues in patients with renal bone disease].

Vitamin D plays a pivotal role in the pathogenesis and treatment of renal bone disease. Vitamin D levels decline in the early phase of renal failure; however, through a compensatory mechanism parathyroid hormone (PTH) stimulates the production of calcitriol to return it to normal circulating concentrations. Nevertheless, resistance to calcitriol is observed and may be related to the decreased presence of the heterodimeric, DNA-binding partner for the vitamin D receptor protein. In end-stage kidney disease (ESKD) the circulating levels of calcitriol are invariably low. The indications of vitamin D therapy are the replacement of the missing hormone versus suppression of hyperparathyroidism requiring daily low-dose oral versus intermittent pulse or oral administration. However, this therapy must be accompanied by careful patient monitoring to avoid hypercalcemia and low bone turnover. Low bone turnover is not merely a histologic entity, but a clinical condition associated with high risk of extraosseous calcifications, in particular in the cardiovascular system, leading to increased morbidity. Thus, determination of bone turnover in patients with ESKD is essential. Bone biopsy is the gold standard to assess bone turnover, however, it is not always available and nephrologists rely on PTH levels. The intact PTH assay measures PTH (1-84) and large C-PTH fragments, which may antagonize the PTH (1-84) effects on bone. An assay that measures exclusively PTH (1-84) has recently become available and a calculated PTH (1-84) /C-PTH fragment ratio has been shown to be the best predictor of bone turnover in patients with ESKD not treated with vitamin D or with other medications known to affect bone metabolism. 22-Oxacalcitriol is a vitamin D analogue that could control serum PTH concentrations without deleterious effects on bone.

English Abstract↗
PubMed2002

[Effects of intravenous and oral OCT on secondary hyperparathyroidism in dogs with chronic renal failure].

In this study, we compare the relative potency of single intravenous OCT (IV OCT) and 1,25 (OH) (2)D(3) [IV 1,25 (OH) (2)D(3)] on serum PTH and ionized calcium (ICa) in dogs with chronic renal failure (CRF). In addition, we examine the efficacy of intermittent IV OCT. A single dose of OCT (5 microg/kg) to uremic dogs suppressed PTH by 81% without a statistical significant change in serum I Ca. On the other hand, any of the effective doses of 1,25 (OH) (2)D(3) on PTH suppression were hypercalcemic. The intermittent administration of OCT (0.1 microg/kg) or 1,25 (OH) (2)D(3) (0.025 microg/kg), 3 times per week IV suppressed serum PTH by 83% or 77%, relatively without hypercalcemia. To evaluate OCT as an oral drag, it was given intermittently (3 times per week) to a group of 6 uremic dogs for a period of 4 weeks. Subsequently it was changed to a daily administration (0.05 microg/kg) for a period of 2 weeks. Finally the dose was reducted to 0.025 microg/kg. Daily OCT 0.05 microg/kg suppressed serum PTH by 67%. Subsequently 0.025 micro/kg maintained serum PTH within the normal range without hypercalcemia for 4 weeks. OCT seems to be promising as a useful agent not only for hemodialysis patients but also for predialysis and CAPD patients. In conclusion, our results suggest that OCT is a useful vitamin D(3) analogue, which has a potentially larger therapeutic window than that of 1,25 (OH) (2)D(3) and which is available for IV/oral, for the management of secondary hyperparathyroidism.

English Abstract↗