A Multi-Compartment Model Capturing the Pharmacokinetics of the Calcimimetic Cinacalcet.

BACKGROUND/AIMS: Chronic kidney disease-mineral bone disorder is a major complication affecting the vast majority of chronic kidney disease patients. A hallmark of the disorder is an altered parathyroid gland biology resulting in secondary hyperparathyroidism. This condition is widely treated by calcimimetics like cinacalcet which act by allosteric activation of the calcium sensing receptor. METHODS: Here, we present a linear multi-compartment model based on physiological principles such as first-pass metabolism and protein binding, which captures all relevant pharmacokinetic parameters of cinacalcet. RESULTS: Due to the linear structure of the model, simulations are numerically stable and allow fast and accurate short or long-term predictions of cinacalcet concentrations in the body. CONCLUSION: The model compartments are physiological meaningful and can be easily adjusted to various conditions like impaired hepatic clearance or different drug administration regimens. Moreover, the model can be easily adapted to specific patient groups.

Impacto de los calcimiméticos en la cirugía del hiperparatiroidismo secundario / Impact of calcimimetics in surgery of secondary hyperparathyroidism

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Separation and quantitative determination of cinacalcet metabolites in urine sample using RP-HPLC after derivation with a fluorescent labeling reagent.

In this investigation, a novel strategy for separation and quantitative determination of four metabolites of cinacalcet (M2a-Glu, M2b-Glu, M7-Gly, and M8-Gly) in human urine is suggested. The analytical assay is based on a pre-column derivation procedure of cinacalcet metabolites with 1-pyrenyldiazomethane (PDAM) as a fluorescent labeling reagent, and subsequently separation and quantitative determination with reverse-phase high-performance liquid chromatography (RP-HPLC) coupled with a fluorescence detector. Metabolites were separated on a Microsorb-MV 100-5 C18 chromatography column (250×4.6mm, 5µm) using acetate buffer (pH 3.5):methanol (30:70 v/v) as mobile phase at a flow rate of 1.0mLmin(-1). The method was fully validated in terms of linearity (r(2)>0.996; 1-10ngmL(-1)), precision (both intra-day and inter-day; RSD<6.2%), accuracy (92-110%), specificity, robustness (0.15%

Calcium-lowering medications in patients with primary hyperparathyroidism: intraoperative findings and postoperative hypocalcemia.

BACKGROUND: We analyzed how calcium-lowering medications (CLMs) influenced surgical findings in patients with primary hyperparathyroidism. METHODS: A retrospective review was conducted of 281 patients undergoing surgery for primary hyperparathyroidism. Logistic regression evaluated the relationship between CLM and surgical findings. A mixed-effects model determined the influence of CLMs on these curves. RESULTS: We found that CLM (P = .018) and a higher serum calcium level (P = .018) were variables making 4-gland hyperplasia less likely. Analysis of intraoperative parathyroid hormone (IOPTH) plots revealed that CLMs altered the kinetics (P = .043). However, the 2 groups did not differ in the number of measurements necessary for a 50% decrease in IOPTH levels. Multivariate logistic regression also revealed that patients taking more than one CLM had an increased association with postoperative hypocalcemia (P = .018). CONCLUSIONS: Although CLM contributed to differences in IOPTH curves, their use does not require changing standard IOPTH protocol but should alert the surgeon to the risk of postoperative hypocalcemia.