PMID- 28160190
OWN - NLM
STAT- MEDLINE
DCOM- 20170410
LR  - 20181202
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Linking)
VI  - 37
IP  - 4
DP  - 2017 Apr
TI  - Changes in Cardiac Function After a Single Intravenous Administration of CKD-712 
      in Healthy Male Volunteers.
PG  - 393-403
LID - 10.1007/s40261-017-0494-3 [doi]
AB  - BACKGROUND AND OBJECTIVES: CKD-712, a candidate treatment for septic shock, acts 
      by increasing cardiac output. This study investigated changes in the 
      pharmacodynamics, pharmacokinetics, and tolerability of CKD-712 after a single 
      intravenous administration. METHODS: A dose-block-randomized, double-blind, 
      placebo-controlled, single-dose escalation study was conducted in 44 healthy 
      subjects receiving 20, 40, 80, 160, 240, or 320 mug/kg CKD-712 or placebo. 
      Pharmacodynamics were evaluated using computerized impedance cardiography, vital 
      signs, platelet aggregation, and bleeding time. Serial blood and urine samples 
      for pharmacokinetic analysis were collected up to 12 and 24 h, respectively, 
      after the initiation of intravenous drug infusion. Tolerability assessments were 
      performed throughout the study. RESULTS: The area under the effect-time curve of 
      the cardiac index (AUEC(CI)) and systolic blood pressure (AUEC(SBP)) changed 
      significantly with the 160 and 320 microg/kg doses of CKD-712 compared with placebo. 
      Furthermore, the AUEC(CI) and AUEC(SBP) tended to increase as the systemic 
      exposure of CKD-712 increased from 20 to 240 microg/kg. The frequency of drug-related 
      adverse events (AEs), including cardiovascular symptoms, was higher with the 
      320 microg/kg dose. CONCLUSION: The pharmacological effects and on-target AEs of 
      CKD-712 increased relative to the dose increments. The results of this study 
      suggest that potentially therapeutic doses of CKD-712 could range from 160 to 
      240 mug/kg.
FAU - Park, Sang-In
AU  - Park SI
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
FAU - Kim, JaeWoo
AU  - Kim J
AD  - Clinical Trials Center, Chungnam National University Hospital, Daejeon, Republic 
      of Korea.
FAU - Yu, Kyung-Sang
AU  - Yu KS
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
FAU - Jang, In-Jin
AU  - Jang IJ
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
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. leejh413@snu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (Tetrahydroisoquinolines)
RN  - 0 (YS 49)
SB  - IM
MH  - Adult
MH  - Blood Pressure/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Middle Aged
MH  - Tetrahydroisoquinolines/*administration & dosage/pharmacology
MH  - Young Adult
EDAT- 2017/02/06 06:00
MHDA- 2017/04/11 06:00
CRDT- 2017/02/05 06:00
PHST- 2017/02/06 06:00 [pubmed]
PHST- 2017/04/11 06:00 [medline]
PHST- 2017/02/05 06:00 [entrez]
AID - 10.1007/s40261-017-0494-3 [pii]
AID - 10.1007/s40261-017-0494-3 [doi]
PST - ppublish
SO  - Clin Drug Investig. 2017 Apr;37(4):393-403. doi: 10.1007/s40261-017-0494-3.