In vitro suppression of parathyroid hormone secretion by 22‐oxa‐calcitriol in human parathyroid hyperplasia due to uraermia

Sato, Keisuke; Tominaga, Yoshihiro; Ichikawa, Fumihiko; Uchida, Kazuharu; Takezawa, Junichi; Tsuchiya, Takeshi; Kubodera, Noboru

doi:10.1046/j.1440-1797.1998.d01-28.x

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…Next, the mechanisms underlying the suppression of parathyroid function by PMIT were studied. As one of the mechanisms, OCT was shown to suppress the synthesis and secretion of PTH, as proven by the reduction in the PTH mRNA level [7,8,13]. The in vivo effect of the suppression of PTH synthesis and secretion by PMIT was observed in this study (Figs.…”

Section: Discussionsupporting

confidence: 65%

“…Maxacalcitol (22-oxacalcitriol; OCT) is an analog of 1,25-dihydroxy vitamin D 3 (1,25-D 3 ) and has been shown to strongly suppress parathyroid function dose dependently and to improve bone disorder caused by SHPT in chronic dialysis patients [5,6]. Experimentally, it has been proved that OCT suppresses PTH mRNA expression in uremic rats without causing hypercalcemia and prevents the decrease in the vitamin D receptor (VDR) expression level in parathyroid gland as well as that of 1,25-D 3 [7][8][9]. Thus, we developed a direct percutaneous injection therapy of maxacalcitol (PMIT) into parathyroid glands.…”

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confidence: 99%

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Percutaneous maxacalcitol injection therapy regresses hyperplasia of parathyroid and induces apoptosis in uremia

Shiizaki¹,

Hatamura²,

Negi³

et al. 2003

Kidney International

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Section: Discussionsupporting

confidence: 65%

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confidence: 99%

Percutaneous maxacalcitol injection therapy regresses hyperplasia of parathyroid and induces apoptosis in uremia

Shiizaki¹,

Hatamura²,

Negi³

et al. 2003

Kidney International

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“…From the final PD parameter estimates (▶ Table 3), the estimated EC 50 of iPTH and cCa was 1.06 × 10 − 4 and 1.83 × 10 − 3 pg/mL, respectively (▶ Table 3). These estimate values are quite low, but they are similar to the effective concentration of maxacalcitol in in vitro pharmacology studies [13].…”

Section: Discussionsupporting

confidence: 65%

Maxacalcitol Pharmacokinetic–Pharmacodynamic Modeling and Simulation for Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis

Fukazawa-Shinotsuka¹,

Saito²,

Abe³

et al. 2021

Drug Res (Stuttg)

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Background Maxacalcitol was approved in Taiwan in 2018 as the first active vitamin D3 injection for secondary hyperparathyroidism (SHPT) in patients on maintenance hemodialysis. However, no data from any clinical study with maxacalcitol in Taiwanese patients is available. Objectives This analysis aimed to evaluate the profiles of parathyroid hormone (PTH) and calcium (Ca) concentrations in Taiwanese SHPT patients on hemodialysis and maxacalcitol. Methods We developed population pharmacokinetic (PK) and pharmacodynamic (PD) models using a modeling and simulation approach. The data for these analyses were obtained from two studies: a clinical pharmacology study in Japanese patients and an ethnic comparison study in healthy Japanese and -Taiwanese volunteers. We then conducted a simulation study with a PK-PD model comprising the PK and PD models developed here. Results Serum maxacalcitol concentration profile was modeled using a two-compartment model that took into consideration the distribution of concentrations below the lower limit of quantification. An ethnic difference in clearance was included in the PK model as a covariate. A PD model that used a PTH/Ca feedback loop best described the observed data. There were no significant differences in Ca or PTH concentrations between Taiwanese and Japanese based on the simulation results from our PK-PD model, even though maxacalcitol exposure was approximately 40% higher in Taiwanese than in Japanese. Conclusions On the basis of these population PK and PD analyses and the clinical study conducted in Japan, there is no clinically relevant difference between Taiwanese and Japanese in terms of serum Ca or PTH levels.

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“…Moreover, maxacalcitol is an analog of 1,25-dihydroxyvitamin D 3 (1,25-D 3 ) and has been shown to suppress parathyroid function dose-dependently and to improve bone disorder caused by SHPT in chronic dialysis patients [10,11,12,13]. Experimental studies have confirmed that maxacalcitol suppresses PTH mRNA expression in uremic rats without causing hypercalcemia and prevents the decrease in the expression level of vitamin D receptor (VDR) in parathyroid gland as well as that of 1,25-D 3 [14,15,16]. Although maxacalcitol has been recently developed as a new vitamin D 3 and its efficacy is anticipated in SHPT [13, 17, 18], there have been few reports on the usefulness of combination therapy of intravenous maxacalcitol and selective PEIT.…”

Section: Introductionmentioning

confidence: 99%

Combination Therapy of Intravenous Maxacalcitol and Percutaneous Ethanol Injection Therapy Lowers Serum Parathyroid Hormone Level and Calcium × Phosphorus Product in Secondary Hyperparathyroidism

Tanaka

Itoh²,

Matsushita³

et al. 2005

Nephron Clin Pract

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Background: Percutaneous ethanol injection therapy (PEIT) is an alternative treatment for secondary hyperparathyroidism (SHPT). Although maxacalcitol has been recently developed as a new vitamin D₃ and its efficacy is anticipated in SHPT, there are only few reports on the usefulness of combination therapy of intravenous maxacalcitol and selective PEIT. Methods: The study population comprised 10 hemodialysis patients (6 males and 4 females, mean age; 51.5 ± 13.5 years, mean HD period 13.7± 3.5 years), with high intact-PTH level (>400 pg/ml) and 1 or 2 enlarged parathyroid glands detected by power Doppler ultrasonography. Intravenous maxacalcitol therapy commenced one week after PEIT at 15 µg/week. The effect of combination therapy was monitored by measuring intact-PTH, serum Ca and P, bone metabolic markers, parathyroid gland volume and bone mineral density, prior to and at 6 and 12 months after PEIT. Results: Successful control of intact-PTH, bone metabolic markers and parathyroid gland volume was achieved using the combination therapy. Serum P and Ca×P productweresignificantly decreased 12 months after PEIT. The mean values of serum intact-PTH, P and Ca×P product fulfilled all of the K/DOQI guidelines at 12 months after PEIT. None of the patients developed complications related to PEIT-maxacalcitol therapy during 12 months following PEIT. Conclusion: Combination therapy of intravenous maxacalcitol therapy and selective PEIT is safe and effective for the treatment of refractory SHPT. This combination therapy results in suppression of PTH secretion, regression of parathyroid hyperplasia and the control of Ca×P product, which may prevent calcific uremic arteriolopathy in dialysis patients.

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In vitro suppression of parathyroid hormone secretion by 22‐oxa‐calcitriol in human parathyroid hyperplasia due to uraermia

Cited by 6 publications

References 26 publications

Percutaneous maxacalcitol injection therapy regresses hyperplasia of parathyroid and induces apoptosis in uremia

Percutaneous maxacalcitol injection therapy regresses hyperplasia of parathyroid and induces apoptosis in uremia

Maxacalcitol Pharmacokinetic–Pharmacodynamic Modeling and Simulation for Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis

Combination Therapy of Intravenous Maxacalcitol and Percutaneous Ethanol Injection Therapy Lowers Serum Parathyroid Hormone Level and Calcium × Phosphorus Product in Secondary Hyperparathyroidism

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