Abstract
BACKGROUND AND OBJECTIVES Secondary hyperparathyroidism is a common consequence of chronic kidney disease. Cinacalcet (Sensipar(®)) is often prescribed in combination to reduce elevated levels of parathyroid hormone, calcium and phosphorus. The objective of this study was to assess the effects of concomitantly administered therapies of calcium carbonate (CaCO(3); TUMS(®)), sevelamer hydrochloride (HCl; Renagel(®)) and pantoprazole sodium (Protonix(®)) on the pharmacokinetics and safety of cinacalcet in healthy subjects. METHODS Three randomized, open-label, two-way crossover pharmacokinetic studies were conducted in healthy subjects. Participants received single doses of cinacalcet alone or in combination with either CaCO(3), sevelamer HCl or pantoprazole. The pharmacokinetic profile of cinacalcet was characterized. Safety assessments including adverse event reporting, changes in vital signs and clinical laboratory measurements were conducted throughout the studies. RESULTS The 90 % confidence intervals for the area under the concentration-time curve from time zero to the last quantifiable concentration (AUC(last)), area under the concentration-time curve from time zero to infinity (AUC(0-∞)) and maximum plasma concentration (C(max)) of cinacalcet were within the accepted range of 80-125 % for both CaCO(3) and sevelamer HCl co-administration with cinacalcet. No severe or serious adverse events or clinically relevant changes in physical or laboratory findings occurred during the studies. CONCLUSION The pharmacokinetic parameters of cinacalcet were not affected by co-administration of CaCO(3), sevelamer HCl or pantoprazole. Co-administration of these agents with cinacalcet does not require an adjustment of the dose of cinacalcet.
