Abstract

Objective: Few studies have focused on the effects of dialysis on cinacalcet. In addition, there is no data available on hemodiafiltration (HDF) all over the world. Therefore, we studied the pharmacokinetics (PK) and pharmacodynamics (PD) of cinacalcet in patients undergoing hemodialysis (HD) or HDF to provide more guiding information on its use in these patients, especially in China. Materials and methods: In this open-label, single-dose, single-center study of 7 patients with renal failure who underwent dialysis, patients were randomly allocated to two groups consisting of 4 and 3 patients who received low-flux HD and HDF treatments, respectively. All participants underwent dialysis for 4 hours immediately after receiving single oral doses of a 25 mg cinacalcet tablet. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and electrochemical luminescence (EI) were used to determine the cinacalcet plasma concentrations and intact parathyroid hormone (iPTH) serum levels, respectively. Results: Peak concentration (C_max) and area under the curve (AUC) from time 0 to 24 hours (AUC_0–24h) of the low-flux HD therapy group were 21.8 ± 18.6 ng/mL and 145.3 ± 91.8 ng×h/mL, respectively, which were similar to those of the HDF group (30.9 ± 7.9 ng/mL and 161.6 ± 26.5 ng×h/mL, respectively). iPTH concentrations of the HD therapy group decreased after cinacalcet administration and increased following its clearance. However, iPTH levels of subjects receiving HDF therapy did not change. Conclusion: Compared with healthy Chinese subjects, patients with renal failure had a higher C_max and AUC_0–24h, slightly prolonged time to C_max (t_max) after administration of the same dose of cinacalcet. On HD treatment day, variation trends of iPTH in Chinese patients and healthy subjects were similar and significantly different from that on the HDF treatment day. Considering the high protein binding rate of cinacalcet, this may lead to the great free-drug clearance during HDF treatment.

*Wenjuan Shi and Xiuyan Tan contributed equally to this research.

Author Details

Authors

• Wenjuan Shi¹*
• Xiuyan Tan¹*
• Zhongdong Li¹
• Minmin Zhang²
• Bihong Huang²
• Fang Lu²
• Jing Jia²
• Jing Chen²
• Mingkang Zhong¹

Departments

• ¹ Department of Pharmacy, and
• ² Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, China

Address


Zhongdong Li

Clinical Pharmacy Laboratory
Huashan Hospital, Fudan University
12 Wu Lu Mu Qi M Road, Shanghai 200040, China
Email: [email protected]

Citation