Pharmacodynamic Modeling of Cinacalcet in Secondary Hyperparathyroidism: Efficacy and Influencing Factors Analysis
Zhizhou Wang, Yexuan Wang, Shun Han, Peixian Chen, Ruo Wu, Chuyao Fang, Junjie Cheng, Yujiao Wu, Tingting Guo, Xin Wen, Lujin LiAbstract
Context
Cinacalcet, the first FDA-approved calcimimetic agent for treating secondary hyperparathyroidism (SHPT), has unclear factors influencing its therapeutic efficacy in clinical practice.
Objective
To establish a pharmacodynamic model for cinacalcet use in SHPT, analyze drug effect distribution and influencing factors, and determine optimal treatment strategy.
Methods
We searched public databases for randomized trials on cinacalcet for SHPT, modeling changes in serum parathyroid hormone (PTH), calcium, and phosphorus postintervention. Key pharmacodynamic parameters and influencing factors were identified, with subgroup analysis for factors not in the covariate model. We also compared cinacalcet efficacy between United States/European Union (30-180 mg) and Asia (25-100 mg) dosage ranges.
Results
Twenty-six studies (4242 subjects) were analyzed. Covariate analysis showed increasing PTH baseline and vitamin D use proportionally affected PTH and calcium decrease. Postintervention, maximum effects were observed with onset times of 0.46, 0.15, and 0.29 months. Subgroup analysis showed factors such as dialysis time, baseline calcium and phosphorus, phosphate binder use, gender proportion, patient ethnicity, blinding, and age influenced PTH, calcium, and phosphorus decrease. The efficacy of cinacalcet at a dosage of 25 to 100 mg in Asian populations was comparable to that observed at a dose range of 30 to 180 mg in Western populations, suggesting that reducing the therapeutic dose of cinacalcet may potentially yield a better benefit–risk ratio.
Conclusion
We established a pharmacokinetic model for cinacalcet in SHPT treatment, providing crucial data for identifying effective patient populations and optimizing treatment strategies.