HPLC法测定盐酸西那卡塞片含量

目的:建立测定盐酸西那卡塞片含量的方法。方法:采用高效液相色谱法。色谱柱为Phenomenex C18,流动相为三乙胺水溶液(pH 8.0)-甲醇(15∶85),流速为1.0 ml/min,检测波长为272 nm,柱温为25℃,进样量为20μl。结果:盐酸西那卡塞检测质量浓度线性范围为39.82³58.3μg/ml(r=0.999 9);平均回收率为99.54%(RSD=0.49%,n=3)。结论:建立的方法操作简便、快捷,结果准确、可靠,可用于盐酸西那卡塞片的质量控制。     

Pharmacokinetics and Pharmacodynamics of Cinacalcet in Patients with Hyperparathyroidism After Renal Transplantation

Cinacalcet is a calcimimetic drug for the treatment of secondary hyperparathyroidism (HPT). In a sequential open-label study, ten patients with persistent HPT after renal transplantation received first 30 and then 60 mg oral cinacalcet once daily over 2 weeks each. Cinacalcet steady state oral clearance was 131.1 ± 20.9 l/h and 92.8 ± 9.5 l/h (mean ± SE) after 30 and 60 mg, respectively. Cinacalcet and parathyroid hormone (PTH) concentrations showed an inverse correlation and were fitted to a simple E_max model (E_max= 80% reduction vs. baseline, EC₅₀= 13 ng/mL). A once daily administration of cinacalcet lowered serum calcium over 24 h without fluctuations. The 8-h fractional urinary excretion of calcium was increased after 60 mg cinacalcet (baseline 0.85 ± 0.17%, 30 mg 1.53 ± 0.35%, 60 mg 1.92 ± 0.37%). Renal function remained stable. Cinacalcet pharmacokinetics and pharmacodynamics showed a pronounced interindividual variability. We conclude that the once daily administration of cinacalcet in patients with secondary HPT after renal transplantation effectively reduced iPTH and serum calcium. The transient calciuria could potentially favor nephrocalcinosis and reduce bone mineral density, suggesting that higher doses of cinacalcet need to be used with caution in renal transplant recipients with severe persistent hyperparathyroidism.     

帕立骨化醇联合西那卡塞治疗血液透析伴继发性甲状旁腺功能亢进的效果研究

目的:研究帕立骨化醇联合西那卡塞治疗维持性血液透析(MHD)继发性甲状旁腺功能亢进(SHPT)患者的疗效和安全性。方法:选取2019年8月至2020年8月本院血液净化中心收治的22例MHD伴SHPT患者为研究对象,所有患者根据全段甲状旁腺激素(iPTH)水平予以帕立骨化醇联合西那卡塞治疗。分别于治疗前及治疗后2、4、8...     

Outcomes in patients with renal hyperparathyroidism requiring cinacalcet pre-operatively followed by parathyroidectomy

Background

Cinacalcet is an effective treatment for renal hyperthyroidism when traditional medical therapy has failed. We studied the impact of pre-operative cinacalcet administration on post-surgical outcomes.

Total Phosphate Elimination is Negatively Associated With Increased Serum Fibroblast Growth Factor 23 Levels in Patients who Undergo Peritoneal Dialysis

As fibroblast growth factor 23 (FGF23) has been shown to induce cardiovascular disease directly in patients with chronic kidney disease, identification of factors and treatments that can modulate serum FGF23 (sFGF23) level is clinically important. This retrospective longitudinal study investigated factors that modulate sFGF23 in 49 patients who underwent peritoneal dialysis (PD). sFGF23 ratio (sFGF23 at 18 months/baseline sFGF23) was used as an indicator of changes in sFGF23 level. Total phosphate elimination was the sum of both renal phosphate excretion and dialysate phosphate elimination. In multivariate analysis, log sFGF23 ratio was associated negatively with total phosphate elimination and the use of cinacalcet at baseline, and positively with the use of vitamin D receptor activators at baseline, even after adjusting for potential confounding factors. Our study indicates that maintaining phosphate elimination can prevent increased sFGF23_, thereby preventing cardiovascular events in patients who undergo PD.     

Dose determination of cinacalcet hydrochloride in Japanese hemodialysis patients with secondary hyperparathyroidism

Cinacalcet hydrochloride is a calcimimetic agent that activates the calcium-sensing receptor on the surface of parathyroid cells and inhibits parathyroid hormone (PTH) secretion. To manage secondary hyperparathyroidism, cinacalcet, which lowers PTH levels without increasing serum calcium, phosphorus and calcium-phosphorus product (Ca x P) levels, may provide a new potential therapy. To identify the optimal starting dose of cinacalcet for Japanese hemodialysis patients with secondary hyperparathyroidism, this double-blind, placebo-controlled, parallel, dose-finding study was conducted. One hundred and twenty Japanese hemodialysis patients with intact PTH levels greater than or equal to 300 pg/mL were randomized into four groups: placebo, and 12.5, 25 and 50 mg of cinacalcet. The treatment period was three weeks followed by a two-week follow-up observation period. Cinacalcet decreased serum intact PTH levels in a dose-dependent manner, and also decreased serum calcium, phosphorus, Ca x P, tartrate-resistant acid phosphatase and osteocalcin levels. The treatment with cinacalcet was generally well tolerated in this study. However, the incidence of treatment-related adverse events, such as gastrointestinal disorders and hypocalcemia, and the rate of withdrawal from the study due to treatment-related adverse events were higher in the 50 mg dose group than in the other groups. On the basis of both efficacy and safety results, 25 mg has been identified as the optimal starting dose of cinacalcet for Japanese hemodialysis patients with secondary hyperparathyroidism.     

HPLC法测定盐酸西那卡塞含量不确定度的评定

摘 要 目的：建立HPLC法测定盐酸西那卡塞的含量,并进行不确定度评定。方法: 采用Inertsil ODS SP(250 mm×4.6 mm,5 μm)为色谱柱,以磷酸盐缓冲液（pH6.5） 乙腈（60∶40）为流动相,流速为1.0 ml瘙
簚min^-1 ,检测波长为272 nm,柱温为30℃,进样量为20 μl;建立计算含量的数学模型,找出影响不确定度的因素,并对各个分量进行评估。结果:西那卡塞与各杂质之间分离良好,在10～100 μg瘙
簚m^-1 浓度范围线性关系良好（r=0.999 9）,平均回收率为101.09%,RSD为0.54%（n=9）,定量限（LOQ）为0.254 μg瘙
簚m^-1 ;盐酸西那卡塞含量扩展不确定度为1.22％,测量结果表示为（100.74 ±1.22） %（k=2）。结论:建立的高效液相色谱法操作简便、快捷、专属性好、结果准确、可靠,可为仿制药制定质量标准提供技术指导;通过分析影响不确定度的因素,找出影响检测结果的主要原因,提高检测结果的可信度。     

西那卡塞与甲状旁腺切除术治疗肾性甲旁亢 患者疗效的Meta分析

目的 采用Meta分析探讨西那卡塞与甲状旁腺切除术治疗肾性甲旁亢的疗效,为临床上治疗肾性甲旁亢的方案选择提供参考。方法 检索PubMed、EMBASE、Cochrane、Webof Science电子数据库,筛选出符合纳入标准的文献,使用Cochrane中心推荐的方法进行文献偏倚风险评估。提取最终纳入文献的相关效应量,使用RevMan5.2软件进行数据合并及分析,评价两种治疗方案的疗效。结果 共检出文献1289篇,纳入符合要求文献共5篇,其中1篇RCT,4篇队列研究,共计肾性甲旁亢患者370例。Meta分析结果示,西那卡塞组与甲状旁腺切除术组血甲状旁腺素（MD=135.48,95% CI:-123.85~394.80,P=0.31）、血钙（MD=-0.08,95% CI:-0.27~0.10,P=0.37）、血磷（MD=-0.02,95% CI:-0.16~0.12,P=0.78）、血碱性磷酸酶（MD=56.66,95% CI:-75.42~188.75,P=0.40）比较,差异均无统计学意义（P＜0.05）。结论 西那卡塞与甲状旁腺切除术治疗肾性甲旁亢相比,在控制血甲状旁腺素、血钙、血磷、血碱性磷酸酶的效果上无差异,疗效相当。     

Cinacalcet impact on calcium homeostasis and bone remodeling in 13 renal transplanted patients with hyperparathyroidism and hypercalcaemia

The purpose of the study is to assess the impact of cinacalcet on calcium and bone remodeling, in post-renal transplanted patients with persistent hypercalcaemia secondary to hyperparathyroidism. Thirteen renal-transplanted adult recipients with a glomerular filtration rate over 30 ml/min/1.73 m², a total serum calcium > 2.60 mmol/l with ionized calcium > 1.31 mmol/l and a parathyroid hormone serum level over 70 pg/ml, were treated with cinacalcet for 4 months followed by a 15-day wash out. The results show that cinacalcet lowers significantly total and ionized calcium respectively from 2,73 (2,67-2,86) to 2,31 (2,26-2,37) mmol/l (P < 0.05) and from 1,39 (1,37-1,47) to 1,21 (1,15-1,22) mmol/l (P < 0.05) with no alteration of the 24-hour urine calcium/creatinine ratio and no significant expected PTH serum level suppression (153 [115-214,9] and 166 [122-174] pg/ml). On the other hand, fasting urine calcium was significantly decreased from 0,61 (0,27-1,02) to 0,22 (0,15-0,37) (P < 0.05) and bone-specific alkaline phosphatases increased from 20,5 (13-46,6) to 33,8 (12-58,9) ng/ml, upon cinacalcet treatment. After its discontinuation, all these effects were reversible. In conclusion, cinacalcet normalizes total and ionized calcium in renal-transplanted recipients with hypercalcemia secondary to hyperparathyroidism through a mechanism that could be independent of PTH serum level suppression. The increase in bone-specific alkaline phosphatases, biochemical markers of bone accretion and the significant decrease in fasting urine calcium suggest the possibility of a beneficial impact of cinacalcet on bone remodeling.