title: Effects of calcium carbonate, sevelamer hydrochloride or pantoprazole on the pharmacokinetics of cinacalcet.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Early Development, Department of Medical Sciences, Amgen Inc., One Amgen Center Dr., Thousand Oaks, CA, 91320, USA, dpadhi@amgen.com.
authors.forename: Desmond
authors.initials: D
authors.lastname: Padhi
authors.forename: Robert
authors.initials: R
authors.lastname: Harris
authors.forename: John T
authors.initials: JT
authors.lastname: Sullivan
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000493:pharmacokinetics*; D000293:Adolescent; D000328:Adult; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics*; D002119:Calcium Carbonate / Q000493:pharmacokinetics*; D002614:Chelating Agents / Q000493:pharmacokinetics*; D000069449:Cinacalcet; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000493:pharmacokinetics*; D000077402:Pantoprazole; D011073:Polyamines / Q000493:pharmacokinetics*; D000069603:Sevelamer; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D002614:Chelating Agents; D009281:Naphthalenes; D011073:Polyamines; D000069603:Sevelamer; D000077402:Pantoprazole; D002119:Calcium Carbonate; D000069449:Cinacalcet