PMID- 22503212
OWN - NLM
STAT- MEDLINE
DCOM- 20120924
LR  - 20181201
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 34
IP  - 5
DP  - 2012 May
TI  - 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.
PG  - 1160-9
LID - 10.1016/j.clinthera.2012.03.058 [doi]
AB  - BACKGROUND: Cinacalcet (KRN1493) was developed to manage secondary 
      hyperparathyroidism in patients with chronic kidney disease. The characteristics 
      of cinacalcet have not been studied in the Korean population. OBJECTIVE: The aim 
      of this study was to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) 
      properties and tolerability of single-dose cinacalcet 50 to 100 mg in healthy 
      male Korean subjects for the purposes of a New Drug Application package for the 
      Korean Food and Drug Administration. METHODS: A randomized, open-label, single 
      ascending-dose, parallel-group study was conducted in healthy male Korean 
      subjects. Subjects were randomly assigned to receive a single oral dose of 
      cinacalcet 50, 75, or 100 mg. Serial blood samples for PK/PD analysis were taken 
      for up to 96 hours after administration. Plasma cinacalcet concentrations were 
      analyzed by HPLC-MS/MS. PK parameters were determined using noncompartmental 
      methods. Plasma intact parathyroid hormone (iPTH) concentrations, 
      albumin-corrected serum calcium concentrations, and serum phosphorus 
      concentrations were measured for PD evaluation. For the evaluation of 
      tolerability, adverse events (AEs) were collected using investigators' 
      questionnaires, subjects' spontaneous reports, clinical laboratory tests, ECG, 
      and physical examinations including vital sign measurements. RESULTS: Sixteen 
      subjects in the 50-mg group, 16 in the 75-mg group, and 6 in the 100-mg group 
      completed the study and were included in the PK/PD analysis. The mean (SD) age, 
      height, and weight of the study population were 4.3 (3.0) years, 174.8 (4.9) cm, 
      and 68.2 (7.5) kg, respectively. The median T(max) value in each of the 3 dose 
      groups was 6.0 hours. Mean C(max) values in the 50-, 75-, and 100-mg dose groups 
      were 12.0 (5.5), 17.2 (14.9), and 43.1 (15.5) mug/L; mean AUC(0-infinity) values were 
      126.6 (56.4), 184.3 (87.9), and 417.4 (169.9) mug . h/L. Characteristics were not 
      linear, based on the data over the dose range of 50 to 100 mg. Mean plasma iPTH 
      concentrations in the 50-, 75-, and 100-mg dose groups were decreased from 
      baseline by 64.0% (11.7%), 63.1% (14.6%), and 70.6% (6.3%). Albumin-corrected 
      serum calcium concentrations displayed patterns similar to those of the plasma 
      iPTH concentrations. Sixteen AEs were reported in 11 subjects. No clinically 
      significant abnormalities were observed in the tolerability assessments. 
      CONCLUSIONS: A single oral dose of cinacalcet was well-tolerated up to 100 mg in 
      this small, selected population of healthy male Korean subjects. In addition, the 
      PK characteristics of cinacalcet and its accompanying PD changes-the decreases in 
      the concentrations of plasma iPTH and albumin corrected serum calcium-were 
      demonstrated in the same population. ClinicalTrials.gov identifier: NCT00942773.
CI  - Copyright (c) 2012 Elsevier HS Journals, Inc. All rights reserved.
FAU - Lee, SeungHwan
AU  - Lee S
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
FAU - Gu, Namyi
AU  - Gu N
FAU - Kim, Bo-Hyung
AU  - Kim BH
FAU - Lim, Kyoung Soo
AU  - Lim KS
FAU - Shin, Sang-Goo
AU  - Shin SG
FAU - Jang, In-Jin
AU  - Jang IJ
FAU - Yu, Kyung-Sang
AU  - Yu KS
LA  - eng
SI  - ClinicalTrials.gov/NCT00942773
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120413
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Naphthalenes)
RN  - 0 (Parathyroid Hormone)
RN  - 0 (Serum Albumin)
RN  - 27YLU75U4W (Phosphorus)
RN  - SY7Q814VUP (Calcium)
RN  - UAZ6V7728S (Cinacalcet)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Area Under Curve
MH  - Calcium/*blood
MH  - Chromatography, High Pressure Liquid
MH  - Cinacalcet
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Male
MH  - Naphthalenes/*administration & dosage/pharmacokinetics/pharmacology
MH  - Parathyroid Hormone/*blood
MH  - Phosphorus/*blood
MH  - Republic of Korea
MH  - Serum Albumin/metabolism
MH  - Tandem Mass Spectrometry
MH  - Young Adult
EDAT- 2012/04/17 06:00
MHDA- 2012/09/25 06:00
CRDT- 2012/04/17 06:00
PHST- 2011/12/25 00:00 [received]
PHST- 2012/03/20 00:00 [revised]
PHST- 2012/03/27 00:00 [accepted]
PHST- 2012/04/17 06:00 [entrez]
PHST- 2012/04/17 06:00 [pubmed]
PHST- 2012/09/25 06:00 [medline]
AID - S0149-2918(12)00238-X [pii]
AID - 10.1016/j.clinthera.2012.03.058 [doi]
PST - ppublish
SO  - Clin Ther. 2012 May;34(5):1160-9. doi: 10.1016/j.clinthera.2012.03.058. Epub 2012 
      Apr 13.