Pharm acology
Chemotherapy 1992;38:150-154
T. Uchibayashi H. Hisazumi
a
a
/. K m c y a m *
Diffusion of Tosufloxacin into
_
,
Prostatic T issue
K Kumanob
Key Words
Abstract
Tosufloxacin Prostatic tissue Prostatectomy
The diffusion of tosufloxacin (TFLX) into the prostatic tissue was studied in 25 patients with benign prostatic hypertrophy. TFLX concentrations in the serum and prostatic tissue were measured at scheduled intervals after oral administration of 450 mg of TFLX on the day before surgery, followed by admin istration of 150 mg of TFLX immediately before surgery. The mean TFLX levels in prostatic tissue (and tissue/serum levels) at 2, 4 and 6 h were 0.35 ±0.16 pg/g (0.93 ±0.36) in 7 patients, 0.58± 0.92 pg/g (1.10±0.45) in 10 patients and 0.22±0.09 pg/g (0.95 ±0.45) in 8 patients. The TFLX levels in prostatic tissue exceeded the minimum inhibitory concentration for several pathogenic bacteria detected in the infected prostatic fluid. Therefore, TFLX shows promise as a useful drug in the treat ment of bacterial prostatitis and infections developing after prostatic surgery.
Introduction
Since nalidixic acid was introduced for the treatment of bacterial infections, many ana logs of it have been developed. Norfloxacin has greater activity against gram-negative bac teria than either pipemidic acid or miloxacin.
Norfloxacin is also highly active against most gram-positive bacteria (1, 2], Tosufloxacin has recently been developed and has a greater ac tivity and a broader spectrum than norfloxacin or ofloxacin [3-5], In this article, tosufloxacin (TFLX, Ozex®) concentrations in prostatic tissue and serum
Dr. T. Uchifcayashi D epartm ent o f Urology School o f Medicine Kanazawa University, Takaram achi 13-1 Kanazawa 920 (Jap an )
© 1992 S. K arger AG, Basel (XXI9-3157/92/ 0383-0150 $2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 8:48:15 PM
Department of Urology, School of Medicine. Kanazawa University, Kanazawa; Research Laboratory, Toyama Chemical Co., Ltd., Toyama, Japan
Table 1. Characteristics of patients
Group No.
Age, years
Weight, kg
BUN, mg/dl
s-Creat., mg/dl
CCT, ml/min
1 2 3
76.9 ±10.4 76.7 ±5.2 73.0 ±9.0
57.4 ±7.0 54.2 ±7.0 59.0 ±11.0
17.4 ±3.8 16.6 ±2.1 18.0 ±5.0
1.0 ±0.2 1.1 ±0.2 1.0 ±0.2
75.0 ±21.0 66.2 ±17.2 76.9 ±21.0
Data are means ±SD . BUN = Blood urea nitrogen; s-Creat. = serum creatinine; Ccr = creatinine clearance. Group 1: surgery 2h after single oral administration of TFLX 150 mg; group 2: 4h after single oral adminis tration of TFLX 150 mg; group 3: 6 h after single oral administration of TFLX 150 mg.
Materials and Methods Subjects Twenty-five patients were studied who had benign prostatic hypertrophy and had been admitted for pros tatectomy to the Department of Urology at Kanazawa University Hospital or one of its affiliated hospitals. This trial was performed from May to November 1989. Administration o f TFLX One hundred and fifty milligrams of TFLX were administered orally 2 h (group 1,7 patients), 4 h (group 2,10 patients) or 6 h (group 3, 8 patients) before sur gery. Characteristics o f Patients Table 1 shows the average age, weight, blood urea nitrogen, serum creatinine and 24-hour endogenous c rea tin in e clearan ce o f th e p a tie n ts. Six o f th e p a tie n ts
had a creatinine clearance of less than 60 ml/min. Collection o f Serum Blood samples were obtained from all the patients before administration of TFLX on the day of surgery at 1 h before surgery and during prostatectomy. After centrifugal separation, the scrum was frozen and stored at -2 0 °C until the TFLX concentration was measured.
Collection o f Prostatic Tissue Excised prostatic tissue was immediately rinsed several times in physiological saline to minimize the in fluence of TFLX in the urine. Subsequently, the outer parts of the prostatic tissue were excised, and the re maining central core was divided into left, right and middle portions, each of which was frozen and stored at -2 0 °C until the tissue concentrations of TFLX were measured. Measurement o f TFLX Concentration The serum concentration of TFLX was measured by the disk agar diffusion method using the Escherichia coli Kp strain as the indicator organism. After placing the prostatic tissues in a fourfold volume of 0.1 M phos phate buffer (pH 8.0), they were homogenized. After centrifugation at 1,2000 g for 15 min at 4°C, the super natant was used for measuring the TFLX concentra tion.
Results
Serum TFLX Concentration
Figure 1 shows concentrations in fasting patients with benign prostatic hypertrophy af ter receiving 150 mg of TFLX. The mean se rum concentrations 2, 4 and 6 h after taking TFLX were 0.38, 0.43 and 0.24 pg/ml, respec tively. Concentration o f TFLX in Prostatic Tissue
The time course of changes in the prostatic tissue concentrations of TFLX is shown in fig-
151
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 8:48:15 PM
are reported and discussed. This oral antibac terial agent is a new quinolone compound developed in the Research Laboratory of Toyama Chemical Co., Ltd.
ure 2. The mean concentrations 2,4 and 6 h af ter receiving TFLX were 0.35, 0.58 and 0.22 pg/g, respectively. Ratio o f Concentration in the Prostatic Tissue to Serum Concentration
The ratio of the TFLX concentration in the prostatic tissue to the serum concentration (P/S ratio) was 0.93 after 2 h, 1.10 after 4 h and 0.95 after 6 h (table 2). Differences in the TFLX concentrations of the left (25 cases), right (25 cases) and middle (23 cases) portions of the prostatic tissue were analyzed in each group using Student’s t test, with no significant differences found (p
Chemotherapy 1992;38:150-154
T. Uchibayashi H. Hisazumi
a
a
/. K m c y a m *
Diffusion of Tosufloxacin into
_
,
Prostatic T issue
K Kumanob
Key Words
Abstract
Tosufloxacin Prostatic tissue Prostatectomy
The diffusion of tosufloxacin (TFLX) into the prostatic tissue was studied in 25 patients with benign prostatic hypertrophy. TFLX concentrations in the serum and prostatic tissue were measured at scheduled intervals after oral administration of 450 mg of TFLX on the day before surgery, followed by admin istration of 150 mg of TFLX immediately before surgery. The mean TFLX levels in prostatic tissue (and tissue/serum levels) at 2, 4 and 6 h were 0.35 ±0.16 pg/g (0.93 ±0.36) in 7 patients, 0.58± 0.92 pg/g (1.10±0.45) in 10 patients and 0.22±0.09 pg/g (0.95 ±0.45) in 8 patients. The TFLX levels in prostatic tissue exceeded the minimum inhibitory concentration for several pathogenic bacteria detected in the infected prostatic fluid. Therefore, TFLX shows promise as a useful drug in the treat ment of bacterial prostatitis and infections developing after prostatic surgery.
Introduction
Since nalidixic acid was introduced for the treatment of bacterial infections, many ana logs of it have been developed. Norfloxacin has greater activity against gram-negative bac teria than either pipemidic acid or miloxacin.
Norfloxacin is also highly active against most gram-positive bacteria (1, 2], Tosufloxacin has recently been developed and has a greater ac tivity and a broader spectrum than norfloxacin or ofloxacin [3-5], In this article, tosufloxacin (TFLX, Ozex®) concentrations in prostatic tissue and serum
Dr. T. Uchifcayashi D epartm ent o f Urology School o f Medicine Kanazawa University, Takaram achi 13-1 Kanazawa 920 (Jap an )
© 1992 S. K arger AG, Basel (XXI9-3157/92/ 0383-0150 $2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 8:48:15 PM
Department of Urology, School of Medicine. Kanazawa University, Kanazawa; Research Laboratory, Toyama Chemical Co., Ltd., Toyama, Japan
Table 1. Characteristics of patients
Group No.
Age, years
Weight, kg
BUN, mg/dl
s-Creat., mg/dl
CCT, ml/min
1 2 3
76.9 ±10.4 76.7 ±5.2 73.0 ±9.0
57.4 ±7.0 54.2 ±7.0 59.0 ±11.0
17.4 ±3.8 16.6 ±2.1 18.0 ±5.0
1.0 ±0.2 1.1 ±0.2 1.0 ±0.2
75.0 ±21.0 66.2 ±17.2 76.9 ±21.0
Data are means ±SD . BUN = Blood urea nitrogen; s-Creat. = serum creatinine; Ccr = creatinine clearance. Group 1: surgery 2h after single oral administration of TFLX 150 mg; group 2: 4h after single oral adminis tration of TFLX 150 mg; group 3: 6 h after single oral administration of TFLX 150 mg.
Materials and Methods Subjects Twenty-five patients were studied who had benign prostatic hypertrophy and had been admitted for pros tatectomy to the Department of Urology at Kanazawa University Hospital or one of its affiliated hospitals. This trial was performed from May to November 1989. Administration o f TFLX One hundred and fifty milligrams of TFLX were administered orally 2 h (group 1,7 patients), 4 h (group 2,10 patients) or 6 h (group 3, 8 patients) before sur gery. Characteristics o f Patients Table 1 shows the average age, weight, blood urea nitrogen, serum creatinine and 24-hour endogenous c rea tin in e clearan ce o f th e p a tie n ts. Six o f th e p a tie n ts
had a creatinine clearance of less than 60 ml/min. Collection o f Serum Blood samples were obtained from all the patients before administration of TFLX on the day of surgery at 1 h before surgery and during prostatectomy. After centrifugal separation, the scrum was frozen and stored at -2 0 °C until the TFLX concentration was measured.
Collection o f Prostatic Tissue Excised prostatic tissue was immediately rinsed several times in physiological saline to minimize the in fluence of TFLX in the urine. Subsequently, the outer parts of the prostatic tissue were excised, and the re maining central core was divided into left, right and middle portions, each of which was frozen and stored at -2 0 °C until the tissue concentrations of TFLX were measured. Measurement o f TFLX Concentration The serum concentration of TFLX was measured by the disk agar diffusion method using the Escherichia coli Kp strain as the indicator organism. After placing the prostatic tissues in a fourfold volume of 0.1 M phos phate buffer (pH 8.0), they were homogenized. After centrifugation at 1,2000 g for 15 min at 4°C, the super natant was used for measuring the TFLX concentra tion.
Results
Serum TFLX Concentration
Figure 1 shows concentrations in fasting patients with benign prostatic hypertrophy af ter receiving 150 mg of TFLX. The mean se rum concentrations 2, 4 and 6 h after taking TFLX were 0.38, 0.43 and 0.24 pg/ml, respec tively. Concentration o f TFLX in Prostatic Tissue
The time course of changes in the prostatic tissue concentrations of TFLX is shown in fig-
151
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 8:48:15 PM
are reported and discussed. This oral antibac terial agent is a new quinolone compound developed in the Research Laboratory of Toyama Chemical Co., Ltd.
ure 2. The mean concentrations 2,4 and 6 h af ter receiving TFLX were 0.35, 0.58 and 0.22 pg/g, respectively. Ratio o f Concentration in the Prostatic Tissue to Serum Concentration
The ratio of the TFLX concentration in the prostatic tissue to the serum concentration (P/S ratio) was 0.93 after 2 h, 1.10 after 4 h and 0.95 after 6 h (table 2). Differences in the TFLX concentrations of the left (25 cases), right (25 cases) and middle (23 cases) portions of the prostatic tissue were analyzed in each group using Student’s t test, with no significant differences found (p
