Tamsulosin alters levofloxacin pharmacokinetics in prostates derived from rats with acute bacterial prostatitis.
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.
Department of Urology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Guo-Dong
GD
Qin
Ming-Zhao
MZ
Xiao
Yuan-Da
YD
Zhou
Jing
J
Yang
Hai-Xia
HX
He
Yue
Y
He
Yang
Y
Zeng
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004347:Drug Interactions; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000378:metabolism; D064704:Levofloxacin; D008099:Liver / Q000378:metabolism; D008297:Male; D015242:Ofloxacin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D011467:Prostate / Q000378:metabolism; D011472:Prostatitis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage*; D000077409:Tamsulosin
D058668:Adrenergic alpha-1 Receptor Antagonists; D000900:Anti-Bacterial Agents; D013449:Sulfonamides; D064704:Levofloxacin; D015242:Ofloxacin; D000077409:Tamsulosin