Ji Sung Shim1, Jae Hyun Bae2. 1. Department of Urology, Korea University Ansan Hospital, Ansan, Republic of Korea. 2. Department of Urology, Korea University Ansan Hospital, Ansan, Republic of Korea. Electronic address: urobae@genetherapy.or.kr.
Abstract
OBJECTIVE: To evaluate the distribution of a daily phosphodiesterase type 5 inhibitor dose (mirodenafil) in rat plasma and bladder and prostate tissue in a model of atherosclerosis-induced chronic pelvic ischemia. METHODS: Thirty-two 18-week-old male Sprague Dawley rats were divided into two groups. Group I (n = 16) comprised a chronic pelvic ischemia model treated with mirodenafil and group II (n = 16) comprised a sham-operated model also treated with mirodenafil. The mirodenafil concentrations in each organ were measured at specific time points after 14 days of daily mirodenafil administration. The drug distribution ratio of group I to group II of each organ was measured, and the bladder tissue-to-plasma and prostate tissue-to-plasma ratios were calculated. RESULTS: The mean drug concentration in the bladder of the rats in group I did not differ significantly from that of group II after mirodenafil administration. In the prostate, the mean drug concentration of group I was significantly higher than that of group II at 1 and 4 hours after drug administration. The drug concentration was higher in the bladder tissue than in the prostate tissue and the bladder tissue-to-plasma ratio was significantly higher than the prostate tissue-to-plasma ratio. CONCLUSION: Our results suggest that mirodenafil levels might be sufficient in the target tissue after daily treatment in an ischemia-induced aging model. Considering the difficulties of tissue distribution study in human subjects, the results of this investigation provided meaningful evidence of the application of daily doses of mirodenafil for treating lower urinary tract symptoms in an aging population.
OBJECTIVE: To evaluate the distribution of a daily phosphodiesterase type 5 inhibitor dose (mirodenafil) in rat plasma and bladder and prostate tissue in a model of atherosclerosis-induced chronic pelvic ischemia. METHODS: Thirty-two 18-week-old male Sprague Dawley rats were divided into two groups. Group I (n = 16) comprised a chronic pelvic ischemia model treated with mirodenafil and group II (n = 16) comprised a sham-operated model also treated with mirodenafil. The mirodenafil concentrations in each organ were measured at specific time points after 14 days of daily mirodenafil administration. The drug distribution ratio of group I to group II of each organ was measured, and the bladder tissue-to-plasma and prostate tissue-to-plasma ratios were calculated. RESULTS: The mean drug concentration in the bladder of the rats in group I did not differ significantly from that of group II after mirodenafil administration. In the prostate, the mean drug concentration of group I was significantly higher than that of group II at 1 and 4 hours after drug administration. The drug concentration was higher in the bladder tissue than in the prostate tissue and the bladder tissue-to-plasma ratio was significantly higher than the prostate tissue-to-plasma ratio. CONCLUSION: Our results suggest that mirodenafil levels might be sufficient in the target tissue after daily treatment in an ischemia-induced aging model. Considering the difficulties of tissue distribution study in human subjects, the results of this investigation provided meaningful evidence of the application of daily doses of mirodenafil for treating lower urinary tract symptoms in an aging population.
Authors: Zachary E Cullingsworth; Naveen Nandanan; Natalie R Swavely; Konstantin Frolov; Randy Vince; Rebecca Zee; Theodore Cisu; Adam P Klausner; John E Speich Journal: Transl Androl Urol Date: 2021-06