Pharmacokinetic and Pharmacodynamic Properties of the Calcimimetic Agent Cinacalcet (KRN1493) in Healthy Male Korean Subjects: A Randomized, Open-Label, Single Ascending-Dose, Parallel-Group Study

Clinical Therapeutics

Volumn 34, Issue 5, 2012, Pages 1160-1169

  Lee, SeungHwan ^a   Gu, Namyi ^a   Kim, Bo Hyung ^a   Lim, Kyoung Soo ^a   Shin, Sang Goo ^a   Jang, In Jin ^a   Yu, Kyung Sang ^a  

^a Seoul National University College of Medicine   (South Korea)

Author keywords

Cinacalcet; Korean; Pharmacodynamics; Pharmacokinetics; Secondary hyperparathyroidism

Indexed keywords

CALCIUM; CINACALCET; PARATHYROID HORMONE; PHOSPHORUS;

ADULT; AGE; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; BODY HEIGHT; BODY WEIGHT; CALCIUM BLOOD LEVEL; CONTROLLED STUDY; DIARRHEA; DRUG BLOOD LEVEL; DRUG DOSE INCREASE; DRUG PACKAGING; DRUG TOLERABILITY; DYSPEPSIA; ELECTROCARDIOGRAM; EYE PAIN; FECES; FOOD AND DRUG ADMINISTRATION; HEADACHE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN EXPERIMENT; HYPOCALCEMIA; KOREA; LABORATORY TEST; MALE; MASS SPECTROMETRY; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; NOSE CONGESTION; OPEN STUDY; PARALLEL DESIGN; PARATHYROID HORMONE BLOOD LEVEL; PERIPHERAL NEUROPATHY; PHOSPHATE BLOOD LEVEL; PHYSICAL EXAMINATION; QUESTIONNAIRE; RANDOMIZED CONTROLLED TRIAL; RHINORRHEA; SENSORY NEUROPATHY; SIDE EFFECT; SINGLE DRUG DOSE; SNEEZING; TIME TO MAXIMUM PLASMA CONCENTRATION; TINNITUS; VITAL SIGN; VOMITING;

ADMINISTRATION, ORAL; ADULT; AREA UNDER CURVE; CALCIUM; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MALE; NAPHTHALENES; PARATHYROID HORMONE; PHOSPHORUS; REPUBLIC OF KOREA; SERUM ALBUMIN; TANDEM MASS SPECTROMETRY; YOUNG ADULT;

EID: 84860710534     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2012.03.058     Document Type: Article

References (30)

1. Fraser W.D. Hyperparathyroidism. Lancet 2009, 374:145-158.
2. Goodman W.G., Quarles L.D. Development and progression of secondary hyperparathyroidism in chronic kidney disease: lessons from molecular genetics. Kidney Int 2008, 74:276-288.
3. Sprague S.M. Renal bone disease. Curr Opin Endocrinol Diabetes Obes 2010, 17:535-539.
4. Cunningham J. Achieving therapeutic targets in the treatment of secondary hyperparathyroidism. Nephrol Dial Transplant 2004, 19(Suppl 5):V9-V14.
5. Goodman W.G. Calcimimetic agents and secondary hyperparathyroidism: rationale for use and results from clinical trials. Pediatr Nephrol 2003, 18:1206-1210.
6. Brown E.M., MacLeod R.J. Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev 2001, 81:239-297.
7. Nemeth E.F., Steffey M.E., Hammerland L.G., et al. Calcimimetics with potent and selective activity on the parathyroid calcium receptor. Proc Natl Acad Sci U S A 1998, 95:4040-4045.
8. Goodman W.G., Hladik G.A., Turner S.A., et al. The Calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism. J Am Soc Nephrol 2002, 13:1017-1024.
9. Quarles L.D., Sherrard D.J., Adler S., et al. The calcimimetic AMG 073 as a potential treatment for secondary hyperparathyroidism of end-stage renal disease. J Am Soc Nephrol 2003, 14:575-583.
10. Smajilovic S., Sheykhzade M., Holmegard H.N., et al. Calcimimetic, AMG 073, induces relaxation on isolated rat aorta. Vascul Pharmacol 2007, 47:222-228.
11. Lindberg J.S., Moe S.M., Goodman W.G., et al. The calcimimetic AMG 073 reduces parathyroid hormone and calcium x phosphorus in secondary hyperparathyroidism. Kidney Int 2003, 63:248-254.
12. Harris R.Z., Salfi M., Sullivan J.T., Padhi D. Pharmacokinetics of cinacalcet hydrochloride when administered with ketoconazole. Clin Pharmacokinet 2007, 46:495-501.
13. Padhi D., Harris R.Z., Salfi M., et al. Pharmacokinetics and pharmacodynamics of cinacalcet in hepatic impairment: phase I, open-label, parallel-group, single-dose, single-centre study. Clin Drug Investig 2008, 28:635-643.
14. Padhi D., Harris R.Z., Salfi M., Sullivan J.T. No effect of renal function or dialysis on pharmacokinetics of cinacalcet (Sensipar/Mimpara). Clin Pharmacokinet 2005, 44:509-516.
15. Harris R.Z., Padhi D., Marbury T.C., et al. Pharmacokinetics, pharmacodynamics, and safety of cinacalcet hydrochloride in hemodialysis patients at doses up to 200 mg once daily. Am J Kidney Dis 2004, 44:1070-1076.
16. Barman Balfour J.A., Scott L.J. Cinacalcet hydrochloride. Drugs 2005, 65:271-281.
17. Padhi D., Harris R. Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet 2009, 48:303-311.
18. Kumar G.N., Sproul C., Poppe L., et al. Metabolism and disposition of calcimimetic agent cinacalcet HCl in humans and animal models. Drug Metab Dispos 2004, 32:1491-1500.
19. Sai K., Saito Y. Ethnic differences in the metabolism, toxicology and efficacy of three anticancer drugs. Expert Opin Drug Metab Toxicol 2011, 7:967-988.
20. Yin S.J., Ni Y.B., Wang S.M., et al. Differences in genotype and allele frequency distributions of polymorphic drug metabolizing enzymes CYP2C19 and CYP2D6 in mainland Chinese Mongolian, Hui and Han populations. J Clin Pharm Ther September 14, 2011, [Epub ahead of print].
21. Korea good clinical practice (KGCP) guidelines [in Korean] Korea Food and Drug Administration, Accessed January 7, 2011. http://clinicaltrials.kfda.go.kr/guide/laws/board_list.jsp?category_seq=12.2008.
22. Declaration of Helsinki: Ethical principles for medical research involving human subjects World Medical Association, Accessed January 7, 2011. http://www.wma.net/en/30publications/10policies/b3/index.html.
23. Jang Y. Medical Neutrition Therapy 2011, Hyo-Il Books, Seoul, Korea.
24. Nakashima D., Takama H., Ogasawara Y., et al. Effect of cinacalcet hydrochloride, a new calcimimetic agent, on the pharmacokinetics of dextromethorphan: in vitro and clinical studies. J Clin Pharmacol 2007, 47:1311-1319.
25. Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications 2009, Lippincott William & Wilkins, Philadelphia, Pa. 4th ed. M. Rowland, T.N. Tozer (Eds.).
26. Pharmacokinetic-Pharmacodynamic Data Analysis: Concepts and Applications 1997, 770. Apotekarsocieteten, Stockholm, Sweden. 2nd ed. J. Gabrielsson, D. Weiner (Eds.).
27. Pharmacokinetics in Drug Development: Clinical Study Design and Analysis 2004, AAPS Press, Arlington, Va. P.L. Bonate, D. Howard (Eds.).
28. Block G.A., Martin K.J., de Francisco A.L., et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 2004, 350:1516-1525.
29. Walser M. Ion association. I. The effect of multivalent anions on the protein-bound and complexed calcium in serum. J Cell Comp Physiol 1960, 55:245-250.
30. Kemp G.J., Blumsohn A., Morris B.W. Circadian changes in plasma phosphate concentration, urinary phosphate excretion, and cellular phosphate shifts. Clin Chem 1992, 38:400-402.