No effect of renal function or dialysis on pharmacokinetics of cinacalcet (Sensipar/Mimpara).
OBJECTIVE
Cinacalcet (cinacalcet HCl; Sensipar/Mimpara) is a calcimimetic that is a treatment for secondary hyperparathyroidism in patients with renal failure. The objective of this study was to assess the effects of renal function and dialysis on the pharmacokinetics and pharmacodynamics of cinacalcet.


METHODS
Two open-label, single-dose (75 mg) studies of cinacalcet were performed: study 1 examined 36 subjects who had renal function ranging from normal to requiring haemodialysis, and study 2 examined ten subjects who were receiving continuous ambulatory peritoneal dialysis. Cinacalcet plasma concentrations were determined using a liquid chromatography-mass spectrometry/mass spectrometry assay. Cinacalcet pharmacokinetics were assessed using noncompartmental analyses.


RESULTS
Following single-dose administration of cinacalcet, there was no evidence of increasing exposure with increasing degree of renal impairment, and the pharmacokinetic profile was similar for all subjects regardless of whether they were receiving haemodialysis (no difference on dialysis or nondialysis days detected) or peritoneal dialysis. Protein binding of cinacalcet, determined in study 1 only, was similar in all groups and the level of renal function did not affect the pharmacodynamics (as determined by intact parathyroid hormone and calcium levels). No serious adverse events occurred during either study.


CONCLUSIONS
The degree of renal impairment and mode of dialysis do not affect the pharmacokinetics or pharmacodynamics of cinacalcet. Therefore, the dose of cinacalcet does not need to be altered for degree of renal impairment or dialysis modality.
Padhi
Desmond
D
Department of Early Development, Amgen Inc., Thousand Oaks, California, USA. dpadhi@amgen.com
Harris
Robert Z
RZ
Salfi
Margaret
M
Sullivan
John T
JT
D000328:Adult; D000368:Aged; D002118:Calcium / Q000097:blood; D000069449:Cinacalcet; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000009:adverse effects / Q000493:pharmacokinetics*; D010281:Parathyroid Hormone / Q000097:blood; D006435:Renal Dialysis
D009281:Naphthalenes; D010281:Parathyroid Hormone; D002118:Calcium; D000069449:Cinacalcet