Int J Clin Pharmacol Ther. 2012 Dec;50(12):880-8. doi: 10.5414/CP201721.

Assessment of the influence of severe renal impairment on the pharmacokinetics  of mirodenafilin  Korean male volunteers.

Noh YH, Lim HS, Cho SH, Ghim JL, Choe S, Jung JA, Kim MJ, Kim YH, Jin SJ, Kim SB, Park JS, Lee SK, Yang WS, Chang JW, Lee B, Bae KS.

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 AND MATERIALS:

This open-label, single-dose, parallel group clinical study enrolled a total 12 volunteers (6 healthy volunteersand 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.

PMID:

23006442

DOI:

10.5414/CP201721