ABSTRACT
AIM: Secondary hyperparathyroidism (SHPT), a complication of haemodialysis, is commonly treated with calcimimetics. The impact of dialysates containing different calcium (Ca) concentrations on clinical efficacy of calcimimetics are unclear. We examined whether dialysate Ca concentrations influence the efficacy and dosing of etelcalcetide with concomitant drugs. METHODS: We performed post hoc analyses of a 52-week, open-label, multicentre study of etelcalcetide in Japanese SHPT patients to determine whether dialysate Ca influences the therapeutic effects of etelcalcetide with concomitant drugs. We evaluated the differences in serum intact parathyroid hormone (iPTH), corrected Ca (cCa) and phosphate levels among three dialysate Ca concentration groups (2.5, 2.75 or 3.0 mEq/L Ca). Tartrate-resistant acid phosphatase 5b (TRACP-5b) and bone alkaline phosphatase (BAP) levels were also compared. Since the dialysate Ca concentration may influence dose adjustment, we assessed the etelcalcetide and concomitant drug doses. RESULTS: There were no clinically meaningful differences in iPTH, cCa and phosphate levels among the 2.5, 2.75 and 3.0 mEq/L groups (n = 34, 64 and 35, respectively) over 52 weeks. At Week 52, more than 82%, 71% and 67% of patients had iPTH, cCa and phosphate levels within target ranges (60-240 pg/mL, 8.4-10.0 mg/dL and 3.5-6.0 mg/dL, respectively) across the three groups. TRACP-5b and BAP levels decreased by Week 52 regardless of dialysate Ca. Changes in etelcalcetide and concomitant drug doses were generally similar in each group. CONCLUSION: The efficacy and dosing of etelcalcetide with concomitant drugs were essentially unaffected by the dialysate Ca concentration. Patients showed improvements in bone hypermetabolism during treatment.
Subject(s)
Calcification, Physiologic/drug effects , Calcium , Hemodialysis Solutions , Hyperparathyroidism, Secondary , Peptides/administration & dosage , Renal Dialysis , Calcimimetic Agents/administration & dosage , Calcium/analysis , Calcium/blood , Calcium/chemistry , Dose-Response Relationship, Drug , Female , Hemodialysis Solutions/analysis , Hemodialysis Solutions/chemistry , Humans , Hyperparathyroidism, Secondary/blood , Hyperparathyroidism, Secondary/etiology , Hyperparathyroidism, Secondary/prevention & control , Japan/epidemiology , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/therapy , Male , Middle Aged , Parathyroid Glands/drug effects , Parathyroid Hormone/blood , Phosphates/blood , Renal Dialysis/adverse effects , Renal Dialysis/methodsABSTRACT
The high-speed liquid-jet velocity achieved using an injector strongly depends on the piston motion, physical property of the liquid, and container shape of the injector. Herein, we investigate the liquid ejection mechanism and a technique for estimating the ejection velocity of a high-speed liquid jet using a pyro jet injector (PJI). We apply a two-dimensional numerical simulation with an axisymmetric approximation using the commercial software ANSYS/FLUENT. To gather the input data applied during the numerical simulation, the piston motion is captured with a high-speed CMOS camera, and the velocity of the piston is measured using motion tracking software. To reproduce the piston motion during the numerical simulation, the boundary-fitted coordinates and a moving boundary method are employed. In addition, we propose a fluid dynamic model (FDM) for estimating the high-speed liquid-jet ejection velocity based on the piston velocity. Using the FDM, we consider the liquid density variation but neglect the effects of the liquid viscosity on the liquid ejection. Our results indicate that the liquid-jet ejection velocity estimated by the FDM corresponds to that predicted by ANSYS/FLUENT for several different ignition-powder weights. This clearly shows that a high-speed liquid-jet ejection velocity can be estimated using the presented FDM when considering the variation in liquid density but neglecting the liquid viscosity. In addition, some characteristics of the presented PJI are observed, namely, (1) a very rapid piston displacement within 0.1 ms after a powder explosion, (2) piston vibration only when a large amount of powder is used, and (3) a pulse jet flow with a temporal pulse width of 0.1 ms.