NDLI: Pharmacokinetic and Pharmacodynamic Properties of Cinacalcet (KRN1493) in Chinese Healthy Volunteers: A Randomized, Open-label, Single Ascending-dose and Multiple-dose, Parallel-group Study.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Liu, Hongzhong Wang, Hongyun Liu, Tao Jiang, Ji Chen, Xia Gao, Feng Hu, Pei
Spatial Coverage	United States
Description	Country affiliation: China Author Affiliation: Liu H ( Clinical Pharmacology Research Centre, Peking Union Medical College Hospital, Beijing, China.); Wang H ( Clinical Pharmacology Research Centre, Peking Union Medical College Hospital, Beijing, China.); Liu T ( Clinical Pharmacology Research Centre, Peking Union Medical College Hospital, Beijing, China.); Jiang J ( Clinical Pharmacology Research Centre, Peking Union Medical College Hospital, Beijing, China.); Chen X ( Clinical Pharmacology Research Centre, Peking Union Medical College Hospital, Beijing, China.); Gao F ( Kyowa Hakko Kirin China Pharmaceutical Co, Ltd, Shanghai, China.); Hu P ( Clinical Pharmacology Research Centre, Peking Union Medical College Hospital, Beijing, China. Electronic address: hubei@pumch.cn.)
Abstract	PURPOSE: The aim of this study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) properties and safety of single and multiple doses of cinacalcet in Chinese healthy volunteers (HVs) for the purposes of a New Drug Application package for the Chinese Food and Drug Administration. METHODS: In this randomized, open-label, single ascending-dose and multiple-dose, parallel-group study, 42 Chinese HVs were randomized to receive a single oral dose of 25, 50, or 100 mg of cinacalcet and multiple doses of 50 mg of cinacalcet once daily for 7 days. Plasma cinacalcet concentrations were analyzed by HPLC-MS/MS. The PK parameters were assessed with noncompartmental analysis. Plasma intact parathyroid hormone, serum calcium, and phosphorus concentrations were measured for PD evaluation. The safety profile was also assessed. Adverse events (AEs) were noted during the study. FINDINGS: Of the 42 randomized HVs, 41 completed the study per protocol; 1 prematurely discontinued the study because of AEs. Cinacalcet has nonlinear PK properties over a dose range of 25 to 100 mg after a single dose. Mean (SD) Cmax values were 7.68 (4.25), 17 (6.33), and 31.3 (16.42) ng/mL with single doses of 25, 50, and 100 mg of cinacalcet, respectively. Mean (SD) AUC0- last values were 58.4 (25.38), 187 (70.7), and 367 (180.03) hrâng/mL with single doses of 25, 50, and 100 mg of cinacalcet, respectively. Steady state was attained within 7 doses of successive daily administration of 50 mg of cinacalcet. At steady state, the mean (SD) Cmax and AUC0-last values were 20.6 (9.63) ng/mL and 297 (146.15) ngâh/mL. The accumulation ratios of Cmax and AUC (AUCτ/AUC0-24) were 1.21 and 1.32. Plasma intact parathyroid hormone and serum calcium concentrations had similar patterns, both decreased after administration of cinacalcet, whether after single dose or multiple doses. A total of 52 AEs were reported in 20 HVs (47.6%). The most frequently reported AEs after single-dose and multiple-dose cinacalcet administration were hypocalcemia, numbness, dizziness, and muscle soreness. No serious AEs were reported. IMPLICATIONS: Cinacalcet was well tolerated and effective after administration of a single oral dose up to 100 mg and multiple doses of 50 mg of cinacalcet once daily for 7 days. Cinacalcet has nonlinear PK properties over a dose range of 25 to 100 mg after a single dose. PK profiles after multiple doses were similar to those after a single dose with no accumulation. Cinacalcet had similar PK and safety profiles between Chinese and Western HVs at the same dose levels.
File Format	HTM / HTML
ISSN	01492918
Issue Number	2
Volume Number	38
e-ISSN	1879114X
Journal	Clinical Therapeutics
Language	English
Publisher	Elsevier
Publisher Date	2016-02-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Pharmacology Calcium Blood Cinacalcet Hydrochloride Administration & Dosage Parathyroid Hormone Phosphorus Adult Area Under Curve Asian Continental Ancestry Group Chromatography, High Pressure Liquid Pharmacokinetics Pharmacology Dose-response Relationship, Drug Female Humans Longitudinal Studies Male Tandem Mass Spectrometry Methods United States Young Adult Comparative Study Journal Article Randomized Controlled Trial Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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.

Pharmacokinetic interaction of finasteride with tamsulosin hydrochloride: an open-label, randomized, 3-period crossover study in healthy Chinese male volunteers.

Single-dose, randomized, open-label, 2-way crossover study of the pharmacokinetics of amitriptyline hydrochloride 10- and 25-mg tablet in healthy male Korean volunteers.

Pharmacokinetic properties and safety profile of histamine dihydrochloride injection in Chinese healthy volunteers: a phase I, single-center, open-label, randomized study.

Pharmacokinetics of rosuvastatin in healthy Chinese volunteers living in China: a randomized, open-label, ascending single- and multiple-dose study.

Comparative fasting bioavailability of 2 bepotastine formulations in healthy male Chinese volunteers: an open-label, randomized, single-dose, 2-way crossover study.

Bioequivalence and comparison of pharmacokinetic properties of 4-mg tablet formulations of rosiglitazone hydrochloride and rosiglitazone maleate: a single-dose, randomized, open-label, two-period crossover study in healthy adult male Chinese volunteers.

Bioequivalence and pharmacokinetic comparison of a single 200-mg dose of meclofenoxate hydrochloride capsule and tablet formulations in healthy Chinese adult male volunteers: a randomized sequence, open-label, two-period crossover study.

Bioequivalence and pharmacokinetic comparison of two mycophenolate mofetil formulations in healthy Chinese male volunteers: an open-label, randomized-sequence, single-dose, two-way crossover study.

Pharmacokinetic and Pharmacodynamic Properties of Cinacalcet (KRN1493) in Chinese Healthy Volunteers: A Randomized, Open-label, Single Ascending-dose and Multiple-dose, Parallel-group Study.

Similar Documents

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.

Pharmacokinetic interaction of finasteride with tamsulosin hydrochloride: an open-label, randomized, 3-period crossover study in healthy Chinese male volunteers.

Single-dose, randomized, open-label, 2-way crossover study of the pharmacokinetics of amitriptyline hydrochloride 10- and 25-mg tablet in healthy male Korean volunteers.

Pharmacokinetic properties and safety profile of histamine dihydrochloride injection in Chinese healthy volunteers: a phase I, single-center, open-label, randomized study.

Pharmacokinetics of rosuvastatin in healthy Chinese volunteers living in China: a randomized, open-label, ascending single- and multiple-dose study.

Comparative fasting bioavailability of 2 bepotastine formulations in healthy male Chinese volunteers: an open-label, randomized, single-dose, 2-way crossover study.

Bioequivalence and comparison of pharmacokinetic properties of 4-mg tablet formulations of rosiglitazone hydrochloride and rosiglitazone maleate: a single-dose, randomized, open-label, two-period crossover study in healthy adult male Chinese volunteers.

Bioequivalence and pharmacokinetic comparison of a single 200-mg dose of meclofenoxate hydrochloride capsule and tablet formulations in healthy Chinese adult male volunteers: a randomized sequence, open-label, two-period crossover study.

Bioequivalence and pharmacokinetic comparison of two mycophenolate mofetil formulations in healthy Chinese male volunteers: an open-label, randomized-sequence, single-dose, two-way crossover study.

Pharmacokinetic and Pharmacodynamic Properties of Cinacalcet (KRN1493) in Chinese Healthy Volunteers: A Randomized, Open-label, Single Ascending-dose and Multiple-dose, Parallel-group Study.