Vol.63 No.4 July 2015

Investigation for penetration of single-dose levofloxacin 500 mg in prostatic tissue

Takuya Sadahira^1,4), Kouichiro Wada^1,4), Shinya Uehara^1,2), Masumi Yamamoto¹⁾, Ritsuko Mitsuhata¹⁾, Hiroyuki Nose^1,3), Ayano Ishii^1,4), Reiko Kariyama¹⁾, Toyohiko Watanabe^1,4) and Hiromi Kumon^1,4)

¹⁾Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Japan
²⁾Department of Urology, Abiko Toho Hospital
³⁾Department of Urology, St. Mary's Hospital
⁴⁾Okayama Urological Research Group (OURG)

Abstract

Fluoroquinolones are often used as potent antimicrobial agents against urogenital pathogens in many countries, however, in recent years there have been many reports about fluoroquinolone-resistance of Neisseria gonorrhoeae, Escherichia coli, Pseudomonas aeruginosa, etc. The antimicrobial effects of fluoroquinolones depend on serum concentration and the levofloxacin(LVFX) 500 mg tablet became available in Japan in June 2009 in place of the 100 mg tablet, with the dosage conforming more accurately to the pharmacokinetics/pharmacodynamics theory. In this study, we evaluated the penetration of LVFX into prostate tissue after a single administration of 500 mg. The inclusion criteria of this study were patients who were referred for transurethral resection of the prostate(TUR-P) and exclusion criteria were patients with active urogenital infection, a history of treatment with fluoroquinolones within one week, or renal failure. LVFX 500 mg was orally administered 2 hours before TUR-P and 0.5 g of prostate tissue and blood samples were collected at the initiation of resection. Drug concentrations were measured with liquid chromatography-tandem mass spectrometry(LC-MS/MS) and analyzed in terms of patient characteristics and adverse events. The mean age of the 5 patients enrolled was 72.5± 3.5 years. The mean volume of the prostate was 56± 21 mL. The mean preoperative prostate-specific antigen level was 3.56± 2.17 ng/mL. The mean estimated glomerular filtration rate was 65.1± 13.6 mL/min/1.73 m². The mean weight of resected prostate tissue was 25± 13 g. The patients were discharged from the hospital within an average of 7± 3 days after surgery. Neither adverse events probably due to the agent nor postoperative urogenital infection was observed. In one patient, adenocarcinoma with a Gleason score of 3+2 was detected. The mean serum and prostate tissue concentrations of LVFX were 5.97± 0.50 μg/mL and 6.65± 2.95 μg/g, respectively. The mean ratio of the prostate concentration to serum concentration was 1.115± 0.445, showing favorable penetration into prostate tissue even after administration of a high dose of LVFX. Our present study suggests that the oral administration of LVFX 500 mg is clinically safe and useful for prophylaxis against or treatment of infections in the prostate.

Key word

levofloxacin, prostate

Received

December 25, 2014

Accepted

March 6, 2015

Jpn. J. Chemother. 63 (4): 406-410, 2015