PMID- 35221673
OWN - NLM
STAT- MEDLINE
DCOM- 20220404
LR  - 20220531
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 16
DP  - 2022
TI  - Pharmacokinetic Drug Interaction Between Amlodipine and Tadalafil: An Open-Label, 
      Randomized, Multiple-Dose Crossover Study in Healthy Male Volunteers.
PG  - 425-433
LID - 10.2147/DDDT.S348897 [doi]
AB  - PURPOSE: The combined administration of tadalafil, a phosphodiesterase-5 
      inhibitor, and amlodipine, a calcium channel blocker, can be a promising 
      therapeutic option for hypertension patients with erectile dysfunction. This 
      study aimed to examine the pharmacokinetic drug interaction between tadalafil and 
      amlodipine and the tolerability of their combined administration in healthy male 
      subjects. SUBJECTS AND METHODS: Healthy volunteers (N = 24) were randomly 
      assigned to one of the six sequences that consisted of three treatments: 
      tadalafil (5 mg) alone, amlodipine (10 mg) alone, and tadalafil plus amlodipine. 
      The study drugs were administered orally for 9 d, and the collected serial blood 
      samples were analyzed up to 72 h after the last dosing. Pharmacokinetic 
      parameters were calculated using non-compartmental analysis. RESULTS: For 
      tadalafil, geometric mean ratios (GMRs) (90% confidence interval (CI)) of the 
      combined therapy over the monotherapy were 1.57 (1.46-1.68) for AUC(tau,ss) and 
      1.34 (1.24-1.45) for C(max,ss). For amlodipine, the GMRs (90% CI) of AUC(tau,ss) 
      and C(max,ss) were 0.93 (0.90-0.97) and 0.95 (0.91-0.99), respectively. The 
      severity of all observed adverse events (AEs) related to the study drugs was 
      mild, and the frequency of AEs of the combined administration was not 
      significantly different from the monotherapy. CONCLUSION: A substantial 
      pharmacokinetic drug interaction between tadalafil and amlodipine was observed 
      with respect to the concentration of tadalafil when administered concomitantly. 
      However, the dose range of the combined administration of tadalafil and 
      amlodipine in the present study was well tolerated by the subjects.
CI  - (c) 2022 Kim et al.
FAU - Kim, Hyungsub
AU  - Kim H
AUID- ORCID: 0000-0002-8736-1655
AD  - Department of Emergency Medical Services, College of Health Sciences, Eulji 
      University, Seongnam, Republic of Korea.
FAU - Lee, Shi Hyang
AU  - Lee SH
AUID- ORCID: 0000-0002-5565-8278
AD  - Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, 
      University of Ulsan, Seoul, Republic of Korea.
FAU - Jung, Jina
AU  - Jung J
AUID- ORCID: 0000-0002-9982-6560
AD  - Hanmi Pharmaceutical Co. Ltd., Seoul, Republic of Korea.
FAU - Hong, Sunghee
AU  - Hong S
AD  - Hanmi Pharmaceutical Co. Ltd., Seoul, Republic of Korea.
FAU - Lim, Hyeong-Seok
AU  - Lim HS
AUID- ORCID: 0000-0003-1420-8200
AD  - Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, 
      University of Ulsan, Seoul, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20220219
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 1J444QC288 (Amlodipine)
RN  - 742SXX0ICT (Tadalafil)
SB  - IM
MH  - Administration, Oral
MH  - *Amlodipine
MH  - Area Under Curve
MH  - Cross-Over Studies
MH  - Drug Interactions
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Tadalafil
PMC - PMC8865872
OTO - NOTNLM
OT  - amlodipine
OT  - drug interaction
OT  - pharmacokinetics
OT  - tadalafil
OT  - tolerability
COIS- Jina Jung and Junghee Hong are employees of Hanmi Pharmaceutical Co. Ltd. Prof. 
      Dr. Hyeong-Seok Lim reports grants from Hanmi Pharmaceutical Company, outside the 
      submitted work. The other authors report no conflicts of interest in this work.
EDAT- 2022/03/01 06:00
MHDA- 2022/04/05 06:00
PMCR- 2022/02/19
CRDT- 2022/02/28 05:32
PHST- 2021/11/18 00:00 [received]
PHST- 2022/01/26 00:00 [accepted]
PHST- 2022/02/28 05:32 [entrez]
PHST- 2022/03/01 06:00 [pubmed]
PHST- 2022/04/05 06:00 [medline]
PHST- 2022/02/19 00:00 [pmc-release]
AID - 348897 [pii]
AID - 10.2147/DDDT.S348897 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2022 Feb 19;16:425-433. doi: 10.2147/DDDT.S348897. 
      eCollection 2022.