title: Assessment of the influence of severe renal impairment on the pharmacokinetics of mirodenafil in Korean male volunteers.
abstract: OBJECTIVE
  To evaluate and compare the pharmacokinetics and tolerability of a single oral dose of mirodenafil in volunteer patients with severe renal impairment and healthy volunteers.
  
  
  METHODS
  This open-label, single-dose, parallel group clinical study enrolled a total 12 volunteers (6 healthy volunteers and 6 volunteer patients with severe renal impairment). Each volunteer was orally administered 50 mg mirodenafil and serial blood samples were obtained after drug administration to determine the plasma concentration of mirodenafil using LC-MS/MS. The measured individual plasma concentrations were used to calculate the pharmacokinetic parameters using noncompartmental methods. Tolerability was also assessed using measurements of vital signs, clinical chemistry tests, and interviews.
  
  
  RESULTS
  All of the volunteers completed the study with no serious adverse events (AEs). A total of 4 AEs were reported, but all were of mild or moderate intensity and not considered to be related to the study drug. The geometric mean (95% CI) of the terminal half-life (t1/2β) and the apparent clearance (CL/F) values of mirodenafil were 2.2 (1.4 - 3.4) h and 127.2 (95.1 - 170.2) l/h in the volunteer patients, and 3.0 (2.1 - 4.4) h and 136.1 (74.4 - 249.2) l/h in the healthy volunteers, respectively. The geometric mean of the AUC0-t of the volunteer patients was 8% higher and the geometric mean for clearance was 7% lower compared with the healthy volunteers. However, the geometric mean of the Cmax of the volunteer patients was 38% higher than that of the healthy volunteers.
  
  
  CONCLUSIONS
  A single oral 50-mg dose of mirodenafil was well tolerated. Exposure (AUC0-t) to mirodenafil was similar in both healthy volunteers and volunteer patients with severe renal impairment and healthy volunteers.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, University of Ulsan, Seoul, Korea.
authors.forename: Yook-Hwan
authors.initials: YH
authors.lastname: Noh
authors.forename: Hyeong-Seok
authors.initials: HS
authors.lastname: Lim
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Cho
authors.forename: Jong-Lyul
authors.initials: JL
authors.lastname: Ghim
authors.forename: Sangmin
authors.initials: S
authors.lastname: Choe
authors.forename: Jin Ah
authors.initials: JA
authors.lastname: Jung
authors.forename: Mi Jo
authors.initials: MJ
authors.lastname: Kim
authors.forename: Yo Han
authors.initials: YH
authors.lastname: Kim
authors.forename: Seok-Joon
authors.initials: SJ
authors.lastname: Jin
authors.forename: Soon Bae
authors.initials: SB
authors.lastname: Kim
authors.forename: Jung Sik
authors.initials: JS
authors.lastname: Park
authors.forename: Sang Koo
authors.initials: SK
authors.lastname: Lee
authors.forename: Won Seok
authors.initials: WS
authors.lastname: Yang
authors.forename: Jai Won
authors.initials: JW
authors.lastname: Chang
authors.forename: Bongyong
authors.initials: B
authors.lastname: Lee
authors.forename: Kyun-Seop
authors.initials: KS
authors.lastname: Bae
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid; D006801:Humans; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000493:pharmacokinetics*; D011744:Pyrimidinones / Q000009:adverse effects / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000378:metabolism*; D013449:Sulfonamides / Q000009:adverse effects / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D011744:Pyrimidinones; D013449:Sulfonamides; C528396:mirodenafil