Operative Behandlung der Prostata-Erkrankungen
Gatifloxacin GTXa new fluoroquinolone with extended antibacterial activity, is an interesting candidate for the treatment of chronic bacterial prostatitis CBP. Besides the antibacterial spectrum, the concentrations in the target tissues and fluids are crucial for the treatment of CBP. Thus, it was of interest to investigate its penetration into prostatic and seminal fluid.
GTX concentrations in plasma, urine, ejaculate, prostatic and seminal fluid, and sperm cells were determined Release Prostatasekret a high-performance liquid chromatography method after oral intake of a single mg dose in 10 male Caucasian volunteers Release Prostatasekret the fasting state. Simultaneous application of the renal contrast agent iohexol was used to estimate the maximal possible contamination of ejaculate and prostatic and seminal fluid by urine.
GTX was well tolerated. The means standard deviations for the following parameters were as indicated: time to maximum concentration of drug in serum, 1. The gatifloxacin concentrations in ejaculate, seminal fluid, and prostatic fluid were in the range of the corresponding plasma concentrations Release Prostatasekret were 1.
The concentrations in sperm cells 0. The good penetration into prostatic and seminal fluid, the good tolerance, and the previously reported broad Release Prostatasekret spectrum suggest that GTX may be a good alternative for the treatment of chronic bacterial prostatitis. Clinical studies should be performed to confirm this assumption. Fluoroquinolones have already been used successfully in the treatment of chronic bacterial prostatitis CBP and are recommended as first-line treatment Release Prostatasekret this indication 16.
This recommendation is based on their antibacterial activity; on their ability to penetrate into prostatic tissue, prostatic fluid, seminal fluid, and ejaculate; and on clinical studies 6. In the vast majority of patients, bacterial evaluation either fails to identify a pathogen nonbacterial prostatitisor identifies so-called atypical bacteria, like Mycoplasma spp.
These atypical pathogens are, however, not well covered by the antibacterial activity of the classical fluoroquinolones, e. Thus, the treatment of CBP remains a challenging issue, and new fluoroquinolones with improved antibacterial activity also against gram-positive pathogens and Mycoplasma and Chlamydia species, as well as against anaerobes, may be considered for the treatment of CBP.
Gatifloxacin, a new fluoroquinolone antibiotic, has a broad spectrum of activity encompassing both gram-positive and gram-negative organisms, as well as anaerobes 2. It also has activity against Mycoplasma and Chlamydia spp. Since the antibacterial spectrum and the concentrations in the Release Prostatasekret tissues are crucial for the treatment of CBP, it was of interest to investigate its penetration into prostatic and seminal fluid.
The results of this study could serve as a basis for a clinical study protocol dosage selection and estimate of clinical and bacteriological efficacy to test gatifloxacin in the treatment of CBP and vesiculitis.
This was a single-dose, one-way, open-labeled, noncontrolled, single-center, phase I study. The study was approved by the institutional and local ethics committees, and written informed consent was obtained from each volunteer. Ten male Caucasian volunteers, 18 to 33 years old mean age, 23 years with a body weight ranging from 63 to 97 kg mean, 77 kg and a body height ranging from to cm mean, cm were included. The subjects were considered healthy according to history, physical examination, electrocardiogram, and standard laboratory Release Prostatasekret, including hepatitis virus and human immunodeficiency virus screen.
Prior to administration of the study drug, and 24 h after dosing, routine hematology, urine, Release Prostatasekret, and electrocardiogram analyses were repeated. Vital signs blood pressure, pulse rate, and oral temperature were assessed, and each subject underwent a full physical examination.
The subjects had no known or suspected intolerance Release Prostatasekret hypersensitivity to quinolones or related drugs and no evidence or history of psychiatric illness, Release Prostatasekret risk, epilepsy, or alcohol or drug abuse.
Before drug intake drug screening of urine for benzodiazepine, opiate, amphetamine, and cannabis was performed by a rapid enzyme immune assay Boehringer, Mannheim, Germany in the Laboratory Schubach, Passau, Germany. Release Prostatasekret and breath alcohol tests were negative for all subjects before drug intake.
The subjects did not use any medication in the 2 weeks prior to the study, any enzyme-inducing or -inhibiting drug during 2 months prior to the study, or any experimental drugs during 3 months prior to the study start and were not likely to require any medication during the Release Prostatasekret period, except one subject who used a local antiviral cream aciclovir Release Prostatasekret 1 day prior to study for the treatment of herpes labialis.
Six of the subjects reported current tobacco use, while four reported that they had never Release Prostatasekret tobacco. Five subjects reported regular use of alcohol, while five reported that they did not regularly consume Release Prostatasekret i. No recreational Release Prostatasekret or alcohol consumption were allowed during the course of the study, 24 h before drug administration to 48 h postdose.
Subjects were not allowed to consume antacids or other drugs containing zinc, magnesium, or calcium within 6 h of gatifloxacin ingestion. All subjects complied with this. After an overnight fast, baseline urine and blood samples were taken. Subsequently the subjects received one tablet of mg of gatifloxacin product no.
CG; batch no. The tablet Release Prostatasekret taken by the oral route under medical supervision with ml of mineral water, including mouth check to assure swallowing. At the Release Prostatasekret of oral study drug administration, subjects also received 5 ml of a single intravenous dose of the renal contrast medium iohexol Omnipaque; Schering, Berlin, Germanycorresponding to 3, g of iohexol 1.
Standard breakfast and lunch were served 3 and 5 h after drug administration, respectively. Supper was ad libitum. Blood samples were taken immediately prior to and 0. Prostatic fluid was obtained by prostatic massage within 5 days prior to baseline and 4 h after study drug administration. Subsequently, at each occasion of prostatic fluid collection ejaculate was obtained by masturbation.
Ejaculate samples Release Prostatasekret divided: one aliquot was taken without further treatment for the measurement of gatifloxacin Release Prostatasekret in ejaculate and the other aliquot was used to measure the concentration of gatifloxacin in seminal fluid and sperm cells following the separation of seminal fluid from the sperm cells as follows. Subsequent high-performance liquid chromatography HPLC analysis was performed on the perchloric acid layer as described for ejaculate.
After prostatic fluid and ejaculate were obtained, the Release Prostatasekret were allowed to empty their bladders for the first time after drug administration, and the urine 0- to 4-h period was collected.
In addition to the 4-h Release Prostatasekret, urine samples of the 4- to 8-h and Release Prostatasekret to h Release Prostatasekret were also collected from all subjects. All subjects who received a dose of gatifloxacin were included in the evaluation of safety, Release Prostatasekret included review of treatment-emergent, clinical adverse events AEs and laboratory AEs. Prostatic fluid, ejaculate, cell-free seminal fluid, and sperm cell samples were analyzed for gatifloxacin at IBMP, Nürnberg-Heroldsberg, Germany.
Iohexol concentrations in urine, ejaculate, and seminal and prostatic fluid were also determined at Release Prostatasekret. Gatifloxacin was extracted by using a liquid-liquid extraction method at pH 7. Gatifloxacin in urine was analyzed using the same procedure as that for the determination of gatifloxacin in plasma. The limit of quantification was 0. The resulting Release Prostatasekret from linear regressions in plasma and urine were at least 0.
The quality control QC samples were measured and treated in the same manner as subjects' samples. Gatifloxacin in prostatic fluid, ejaculate, cell-free seminal fluid and sperm cells was analyzed by a validated HPLC method with fluorescence Release Prostatasekret at IBMP.
Fifteen microliters of samples were in this way analyzed by HPLC with fluorescence detection. The Release Prostatasekret 3 software release, version 3.
For validation and calibration, ejaculate, seminal fluid, and sperm cell calibration curves using nine standards including a blank sample and sets of spiked QC samples were prepared. The coefficients from linear regressions of the standard curve were at least 0. For prostatic fluid and for sperm cells no calibration curve could be prepared due to the low volume of drug-free prostatic fluid or sperm cells available.
Therefore, prostatic fluid and sperm cell samples were analyzed against the seminal fluid calibration curve. The QC Release Prostatasekret were measured and treated in the same manner as subjects' samples. The method used has been implemented at Release Prostatasekret laboratory.
For human urine three iohexol standards were prepared Using the theoretical concentrations of these standards and measured peak heights, concentrations were determined and clinical samples were analyzed against these standards.
Concentrations of iohexol in clinical urine samples ranged from 0. For validation and calibration, ejaculate and cell-free seminal fluid calibration curves using seven standards including a blank sample and sets of spiked QC samples were prepared. Calibration was performed by weighted reciprocal of standard concentration linear regression. The resulting coefficients from linear progressions were at least 0.
The limit of Release Prostatasekret of iohexol was set to 1. For validation of the iohexol concentration in ejaculate and cell-free seminal fluid, three QC samples for each fluid were prepared.
The gatifloxacin assay was cross-checked for iohexol and the iohexol assay was cross-checked for gatifloxacin, and no interference was found. This result was expected, since iohexol is a polar compound unlikely to be extracted by the solvent used to extract gatifloxacin methylene Release Prostatasekret at pH 2. In addition, the mobile phase used for the assay of gatifloxacin is more polar than that used for iohexol, suggesting that iohexol would elute much earlier than gatifloxacin.
For plasma and urine measurements of gatifloxacin the outputs of the analytical detector were digitized by means of an analog-to-digital converter connected to a personal computer. The signals were identified and processed for peak height calculation with the Turbochrom 4 software. For calibrations, the nominal concentrations associated with Release Prostatasekret measurements were computed through weighted linear regression weighting factor: reciprocal of standard concentration squares.
Concentrations in the subject's samples and the QC samples were calculated using the slope and the intercept obtained from the calibration lines. Concentrations were expressed Release Prostatasekret micrograms of anhydrous gatifloxacin per milliliter of Release Prostatasekret.
The evaluation of the calibration standards of gatifloxacin and iohexol in prostatic fluid, ejaculate, cell-free seminal fluid, and sperm cells was performed by a weighted linear regression reciprocal of standard concentration with Release Prostatasekret concentrations of calibration standards and measured peak height ratios for gatifloxacin concentration or peak heights for iohexol concentrations by employing Turbochrom 3 software version 3.
All statistical calculations were performed on a PC using the program Microsoft Excel version 7. Single-dose, noncompartmental pharmacokinetic parameters of gatifloxacin were calculated for each subject dosed with gatifloxacin according to standard methods by using PHAR-NCA software Innaphase, Paris, France; version 1. The individual concentrations of gatifloxacin in plasma are shown in Fig. The AUC 0—24 was A mean AUC 0—12 has been calculated The mean Release Prostatasekret urinary concentration and cumulative excretion of gatifloxacin are shown in Fig.
Within 12 h on average Given the excreted amount of gatifloxacin Median range plasma concentration amounted to 1. Median ejaculate- seminal fluid- and Release Prostatasekret fluid-to-plasma ratios were 1. Theoretical maximum percent urinary contaminations of ejaculate, seminal fluid, and prostatic fluid were calculated from the iohexol concentrations in urine and the corresponding fluids.
The theoretical maximum percent urinary concentration of the ejaculate ranged between 0. Thus, the highest possible urinary contamination of 0. The measured gatifloxacin concentration of that prostatic fluid was 1. If urinary contamination is assumed as mentioned before, the real concentration in prostatic fluid would have been 1. If all fluid-to-plasma ratios are corrected by this means, the median range true fluid-to-plasma ratios of gatifloxacin can Release Prostatasekret calculated as 1.