PMID- 25336921
OWN - NLM
STAT- MEDLINE
DCOM- 20151009
LR  - 20220321
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 8
DP  - 2014
TI  - Evaluation of the pharmacokinetic and pharmacodynamic drug interactions between 
      cilnidipine and valsartan, in healthy volunteers.
PG  - 1781-8
LID - 10.2147/DDDT.S68574 [doi]
AB  - PURPOSE: Although cilnidipine and valsartan are widely coadministered to patients 
      with hypertension, their drug-drug interaction potential has not been 
      investigated. This study compared the pharmacokinetic (PK), pharmacodynamic (PD), 
      and tolerability profiles of cilnidipine and valsartan, both alone and in 
      combination, in healthy male subjects. PATIENTS AND METHODS: Fifty-four subjects, 
      enrolled into an open-label, single-dose, three-treatment, three-period crossover 
      study, randomly received cilnidipine (10 mg), valsartan (160 mg), or both 
      according to one of six sequences. Blood samples were collected at baseline and 
      up to 24 hours after drug administration in each period. Plasma concentrations of 
      cilnidipine and valsartan were determined by liquid chromatography with tandem 
      mass spectrometry. Maximum plasma concentration (Cmax) and area under the 
      concentration-time curve from 0 to the last measurable time (AUC(last)) were 
      estimated using a noncompartmental method. Tolerability was evaluated by 
      assessing adverse events (AEs), vital signs, electrocardiograms, and clinical 
      laboratory tests. Blood pressure was also measured for PD assessment. RESULTS: A 
      total of 51 subjects completed the study. The PK profile of cilnidipine was not 
      significantly affected by coadministered valsartan; the geometric mean ratio and 
      90% confidence interval (90% CI) of AUC(last) for cilnidipine with and without 
      valsartan was 1.04 (0.98-1.10). Likewise, cilnidipine did not affect the PK of 
      valsartan; the geometric mean ratio (90% CI) of AUC(last) for valsartan with and 
      without cilnidipine was 0.94 (0.83-1.07). Coadministration of cilnidipine and 
      valsartan reduced blood pressure in an additive way. No serious AEs were 
      reported, and both cilnidipine and valsartan were well tolerated. CONCLUSION: 
      Coadministered cilnidipine and valsartan do not cause a significant PK or PD 
      interaction, and they are well tolerated.
FAU - Lee, Jieon
AU  - Lee J
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
FAU - Lee, Howard
AU  - Lee H
AD  - Clinical Trials Center, Seoul National University Hospital, Seoul, Republic of 
      Korea.
FAU - Jang, Kyungho
AU  - Jang K
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
FAU - Lim, Kyoung Soo
AU  - Lim KS
AD  - Department of Clinical Pharmacology and Therapeutics, CHA University School of 
      Medicine and CHA Bundang Medical Center, Seongnam, Republic of Korea.
FAU - Shin, Dongseong
AU  - Shin D
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, 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.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20141008
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Dihydropyridines)
RN  - 0 (Tetrazoles)
RN  - 80M03YXJ7I (Valsartan)
RN  - 97T5AZ1JIP (cilnidipine)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Adult
MH  - Cross-Over Studies
MH  - Dihydropyridines/administration & dosage/blood/*pharmacokinetics
MH  - Drug Interactions
MH  - Drug-Related Side Effects and Adverse Reactions
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Tetrazoles/administration & dosage/blood/*pharmacokinetics
MH  - Valine/administration & dosage/*analogs & derivatives/blood/pharmacokinetics
MH  - Valsartan
MH  - Young Adult
PMC - PMC4199974
OTO - NOTNLM
OT  - antihypertensive drugs
EDAT- 2014/10/23 06:00
MHDA- 2015/10/10 06:00
PMCR- 2014/10/08
CRDT- 2014/10/23 06:00
PHST- 2014/10/23 06:00 [entrez]
PHST- 2014/10/23 06:00 [pubmed]
PHST- 2015/10/10 06:00 [medline]
PHST- 2014/10/08 00:00 [pmc-release]
AID - dddt-8-1781 [pii]
AID - 10.2147/DDDT.S68574 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2014 Oct 8;8:1781-8. doi: 10.2147/DDDT.S68574. eCollection 
      2014.