Tamsulosin alters levofloxacin pharmacokinetics in prostates derived from rats with acute bacterial prostatitis

Abstract

The combination of levofloxacin and α1 adrenergic antagonist treatment is the current preferred choice for both bacterial and non-bacterial prostatitis. The aim of this study is to explore the influence of α1 adrenergic antagonists on the pharmacokinetics of levofloxacin using rat models with acute bacterial prostatitis (ABP) induced by direct injection with Escherichia coli (ATCC25922). A total of 96 model rats were randomly assigned into two groups: the experimental group (treated with both tamsulosin and levofloxacin, n=48) and the control group (treated with levofloxacin and solvents, n=48). Six rats from each group were euthanized to collect blood, liver, kidney and prostate samples at the time points of 0.125, 0.25, 0.5, 1, 2, 4, 8 and 12 h after drug administration. The levofloxacin concentrations were detected by high performance liquid chromatography (HPLC), and the pharmacokinetic parameters were calculated using the 3p97 software program. There were no obvious differences (P>0.05) between the experimental and control groups in the major pharmacokinetic parameters of levofloxacin, including the halftime (t1/2), time to peak (tpeak), clearance rate (CL), maximum concentration (Cmax) and area under the curve (AUC0∼12), in the plasma or in the hepatic and kidney tissues of the model rats. However, in the prostatic tissues, tamsulosin increased the Cmax, prolonged the t1/2 and decreased the CL of levofloxacin (P<0.05). These results indicate that tamsulosin may enhance the effect of levofloxacin in the treatment of bacterial prostatitis without changing the drug concentration in the liver and kidney.

Personalized therapeutics for levofloxacin: a focus on pharmacokinetic concerns

“…The combination therapies were better than antibiotic therapies alone, and the best result was obtained using the LVX + tamsulosin combination 43. The enhanced efficacy may be explained by the finding that tamsulosin could alter the pharmacokinetics of LVX in prostate tissue derived from rats with acute bacterial prostatitis 44. Ninety-six rats with experimental bacterial prostatitis were randomly assigned to two groups, ie, an experimental group (treated with both tamsulosin and LVX, n=48) and a control group (treated with LVX and solvents, n=48).…”

“… 43 The enhanced efficacy may be explained by the finding that tamsulosin could alter the pharmacokinetics of LVX in prostate tissue derived from rats with acute bacterial prostatitis. 44 Ninety-six rats with experimental bacterial prostatitis were randomly assigned to two groups, ie, an experimental group (treated with both tamsulosin and LVX, n=48) and a control group (treated with LVX and solvents, n=48). Tamsulosin increased the C max , prolonged the t 1/2 , and decreased the clearance of LVX ( P <0.05) in the prostatic tissue, despite there being no obvious differences ( P >0.05) between the two model rat groups in terms of the major pharmacokinetic parameters of LVX in plasma or in the hepatic and kidney tissues.…”

A Rapid and Simple High-Performance Liquid Chromatographic Method for Determination of Levofloxacin in Human Plasma

“…In the previous analytical methods [6][7][8][9][10][11][12][13][14][15][16][17], robustness study was not performed. However, in this method, robustness study was conducted to evaluate whether deliberate small changes in HPLC system could or couldn't influence analytical results.…”

“…Most of these method used many kinds of additives as mobile phase component for improving peak shape and resolution i.e. triethylamine [7,[12][13][14], bromide [11], tetramethyl ammonium bromide [8], butadiene styrene brominated ammonium [9], tetrabutylammonium hydrogen sulfate [10], and trifluoroacetic acid [6,15]. The other method was developed under gradient elution using a formic acid 0.05% and methanol as mobile phase component [17], but this method gives relatively long separation time (about 13 min).…”

“…A validated bioanalytical method for quantitative estimation of LEV in human plasma at a pharmacokinetic range approximately 1-20 µg/mL is necessary to conduct the bioequivalence study [5]. A number of analytical methods for quantifying LEV were developed such as highperformance liquid chromatography coupled with ultraviolet (HPLC-UV), fluorescent (HPLC-FL), and tandem mass spectrometry (HPLC-MS/MS) detector [6][7][8][9][10][11][12][13][14][15][16][17]. Most of these method used many kinds of additives as mobile phase component for improving peak shape and resolution i.e.…”