title: Pharmacokinetics and pharmacodynamics of cinacalcet in patients with hyperparathyroidism after renal transplantation.
abstract: 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, EC(50) = 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.
authors.affiliation: Clinic for Nephrology, University Hospital, Rämistrasse 100, Zurich, Switzerland. andreas.serra@usz.ch
authors.forename: A L
authors.initials: AL
authors.lastname: Serra
authors.forename: S C
authors.initials: SC
authors.lastname: Braun
authors.forename: A
authors.initials: A
authors.lastname: Starke
authors.forename: R
authors.initials: R
authors.lastname: Savoca
authors.forename: M
authors.initials: M
authors.lastname: Hersberger
authors.forename: S
authors.initials: S
authors.lastname: Russmann
authors.forename: N
authors.initials: N
authors.lastname: Corti
authors.forename: R P
authors.initials: RP
authors.lastname: Wüthrich
mesh_terms: D019540:Area Under Curve; D002116:Calcitonin / Q000097:blood; D002130:Calcium Phosphates / Q000378:metabolism; D002762:Cholecalciferol / Q000097:blood; D000069449:Cinacalcet; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology; D016030:Kidney Transplantation / Q000009:adverse effects*; D009281:Naphthalenes / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D010281:Parathyroid Hormone / Q000097:blood
chemical_list: D002130:Calcium Phosphates; D009281:Naphthalenes; D010281:Parathyroid Hormone; D002762:Cholecalciferol; D002116:Calcitonin; D000069449:Cinacalcet