Document Detail


The pharmacokinetics of cinacalcet are unaffected following consumption of high- and low-fat meals.
MedLine Citation:
PMID:  17515696     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cinacalcet HCl reduces iPTH, serum calcium, serum phosphorus, and the calcium-phosphorus product in patients with chronic kidney disease and secondary hyperparathyroidism who are receiving dialysis, and reduces elevated serum calcium associated with primary hyperparathyroidism and parathyroid carcinoma. Cinacalcet is administered orally, and thus concomitant administration with food may affect its bioavailability. The objective of this study was to examine the effect of fat and caloric intake on cinacalcet exposure. This phase 1, randomized, open-label, single-dose, 3-period, 3-treatment, 6-sequence crossover study enrolled 30 healthy subjects (19 men, 11 women) to receive a single oral dose of cinacalcet HCl (Sensipar/Mimpara; Amgen Inc. Thousand Oaks, CA) (90 mg) on 3 separate occasions: following a high-fat, high-caloric meal, a low-fat, low-caloric meal, and a 10-hour fast. Blood samples were obtained predose and up to 72 hours postdose for pharmacokinetic (AUCinfinity, Cmax) and safety evaluations. Twenty-nine subjects completed all the 3 treatment conditions. The mean (90% confidence intervals) AUCinfinity following high- and low-fat meals was increased by 68 (48 to 89)% and 50 (33 to 70)%, respectively, relative to fasting. The difference in mean AUCinfinity between high- and low-fat meals was small [12 (9.9-26)%]. The mean tmax of cinacalcet was prolonged in fasting subjects (6 h) in relation to high-fat (4 h) and low-fat (3.5 h) fed subjects. The mean t1/2beta was similar between treatment conditions. Adverse events (AE) were observed at a similar frequency across the treatment conditions [high fat (34%), low fat (23%), and fasting (31%)]; the type of AE did not differ among the treatment conditions. The most common treatment-related AEs were headache 6/30 (20%), nausea 5/30 (17%), and dyspepsia 4/30 (13%) subjects. Administration of cinacalcet with either high- or low-fat meals results in significant increases in exposure, relative to administration under fasting conditions. However, the small differences observed in exposure following the ingestion of the different types of meals suggest that although food has a significant effect, the type of food does not. The observed effect supports the labeling statement that cinacalcet be taken with food, or shortly after a meal.
Authors:
Desmond Padhi; Margaret Salfi; Robert Z Harris
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Publication Detail:
Type:  Clinical Trial, Phase I; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of therapeutics     Volume:  14     ISSN:  1075-2765     ISO Abbreviation:  Am J Ther     Publication Date:    2007 May-Jun
Date Detail:
Created Date:  2007-05-22     Completed Date:  2007-07-19     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  9441347     Medline TA:  Am J Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  235-40     Citation Subset:  IM    
Affiliation:
Department of Early Development/Medical Sciences, Amgen Inc. Thousand Oaks, CA 91320, USA. dpadhi@amgen.com
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MeSH Terms
Descriptor/Qualifier:
Adult
Area Under Curve
Cross-Over Studies
Dietary Fats / pharmacology*
Dose-Response Relationship, Drug
Drug Interactions
Fasting / metabolism
Female
Half-Life
Humans
Male
Metabolic Clearance Rate
Naphthalenes / adverse effects,  blood,  pharmacokinetics*
Chemical
Reg. No./Substance:
0/Dietary Fats; 0/Naphthalenes; UAZ6V7728S/cinacalcet

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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