PMID- 19695390
OWN - NLM
STAT- MEDLINE
DCOM- 20091027
LR  - 20131121
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 31
IP  - 6
DP  - 2009 Jun
TI  - Influence of alcohol on the hemodynamic effects and pharmacokinetic properties of 
      mirodenafil: a single-dose, randomized-sequence, open-label, crossover study in 
      healthy male volunteers in Korea.
PG  - 1234-43
LID - 10.1016/j.clinthera.2009.06.008 [doi]
AB  - BACKGROUND: Mirodenafil is a phosphodiesterase type 5 (PDE-5) inhibitor developed 
      for the treatment of erectile dysfunction. Mirodenafil has the possibility of 
      being administered with alcohol. OBJECTIVE: This study assessed the hemodynamic 
      effects and pharmacokinetic properties of mirodenafil administered with alcohol. 
      METHODS: This single-dose, randomized-sequence, open-label, crossover study was 
      conducted in healthy male volunteers at the Clinical Trials Center, Seoul 
      National University Hospital, Seoul, Korea. Volunteers were randomly allocated to 
      1 of 3 randomized-sequence groups, each of which consisted of 3 administration 
      phases, each separated by a 1-week washout period: oral mirodenafil 100 mg, 
      alcohol 0.5 g/kg, and both. Vital signs (systolic blood pressure [SBP], 
      dia-stolic BP [DBP], and pulse rate) were measured before (baseline) and at 0.5, 
      1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, and 24 hours after administration. 
      Because volunteers were given a standardized meal at 4 hours after mirodenafil 
      and/or alcohol administration, hemody-namic results were assessed using the 
      maximum decrease from baseline during a period of up to 4 hours after 
      administration. For pharmacokinetic assessment, serial blood samples were 
      collected before (baseline) and at 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 
      24 hours after administration. Tolerability was assessed using monitoring of 
      adverse events (AEs), clinical laboratory parameters, and results of 12-lead 
      electrocardiography. RESULTS: A total of 20 subjects participated in the study 
      (mean [range] age, 25.5 years [20-41 years]; weight, 69.8 kg [57.4-87.2 kg]; and 
      height, 174.7 cm [168-186 cm]). Up to 4 hours after the administration of 
      mirodenafil, alcohol, and mirodenafil + alcohol, the mean (SD) maximum decreases 
      in SBP were 8.5 (3.5), 13.5 (7.8), and 15.1 (6.7) mm Hg, respectively, and the 
      maximum decreases in DBP were 6.4 (4.8), 13.3 (7.4), and 13.8 (5.2) mm Hg. 
      Simultaneous administration of mirodenafil + alcohol was associated with 
      additional mean (95% CI) decreases in SBP and DBP of 1.7 mm Hg (-6.0 to 2.6 mm 
      Hg) and 0.6 mm Hg (-4.7 to 3.6 mm Hg) compared with alcohol alone. 
      Pharmacokinetic parameters of mirodenafil were not significantly different when 
      the drug was administered with or without alcohol. The mean (SD) AUC(0-t) values 
      were 842.0 (434.7) ng/mL/h with mirodenafil and 833.4 (398.2) ng/mL/h with 
      mirodenafil + alcohol. The most common AEs considered at least possibly related 
      to study drug were nasal congestion (7 subjects [35%]), headache (3 [15%]), 
      nausea (1 [5%]), and hiccups (1 [5%]). CONCLUSIONS: The concurrent administration 
      of mirodenafil with alcohol was not associated with clinically significant 
      hemodynamic changes in these healthy male volunteers in Korea. The 
      pharmacoki-netics of mirodenafil were not significantly altered by this 
      concurrent administration. Mirodenafil administered with alcohol had a 
      tolerability profile comparable to that of mirodenafil alone.
FAU - Kim, Bo-Hyung
AU  - Kim BH
AD  - Department of Pharmacology and Clinical Pharmacology, Seoul National University 
      College of Medicine and Hospital, Seoul, Korea.
FAU - Yi, SoJeong
AU  - Yi S
FAU - Kim, JaeWoo
AU  - Kim J
FAU - Lim, Kyoung Soo
AU  - Lim KS
FAU - Kim, Kyu-pyo
AU  - Kim KP
FAU - Lee, BongYong
AU  - Lee B
FAU - Shin, Sang-Goo
AU  - Shin SG
FAU - Jang, In-Jin
AU  - Jang IJ
FAU - Yu, Kyung-Sang
AU  - Yu KS
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Phosphodiesterase 5 Inhibitors)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Pyrimidinones)
RN  - 0 (Sulfonamides)
RN  - 3K9958V90M (Ethanol)
RN  - 504G362H0H (mirodenafil)
SB  - IM
MH  - Adult
MH  - Area Under Curve
MH  - Blood Pressure/drug effects
MH  - Cross-Over Studies
MH  - Drug Interactions
MH  - Electrocardiography
MH  - Ethanol/*pharmacology
MH  - Hemodynamics/*drug effects
MH  - Humans
MH  - Korea
MH  - Male
MH  - Phosphodiesterase 5 Inhibitors
MH  - Phosphodiesterase Inhibitors/adverse effects/pharmacokinetics/*pharmacology
MH  - Pyrimidinones/adverse effects/pharmacokinetics/*pharmacology
MH  - Sulfonamides/adverse effects/pharmacokinetics/*pharmacology
MH  - Time Factors
MH  - Young Adult
EDAT- 2009/08/22 09:00
MHDA- 2009/10/29 06:00
CRDT- 2009/08/22 09:00
PHST- 2009/04/22 00:00 [accepted]
PHST- 2009/08/22 09:00 [entrez]
PHST- 2009/08/22 09:00 [pubmed]
PHST- 2009/10/29 06:00 [medline]
AID - S0149-2918(09)00191-X [pii]
AID - 10.1016/j.clinthera.2009.06.008 [doi]
PST - ppublish
SO  - Clin Ther. 2009 Jun;31(6):1234-43. doi: 10.1016/j.clinthera.2009.06.008.