The Study Of Pharmacokinetic Mechanism On The Treatment Of Bacterial Prostatitis By Α₁ -Adrenoceptor Blocking Drugs Combined With Antibacterial Drugs

Objective To study the influence ofα1-adrenoceptor blocking drugs on the pharmacokinetics of antibacterial drugs in the tissue of prostate when they combined to treat bacteral prostatitis in rats.Methods Making the model of bacteral prostatitis with 120 rats,then averagely divided into experimental group and control group randomly. All rats were injected levofloxacin(44mg/kg), then experimental group was given terazosin(0.44mg/kg) for oral administration and control group was solvent. The tissue of prostate was collected after administration 1,3,7.5, 15, 30,60,120,240,480 and 720min,then made into homogenate. The concentr -ation of levofloxacin in tissue of prostate was detected by HPLC method, and pharmacokinetic parameters were calculated with 3p97 software program. Repeating the experiment with tamsulosin(0.018mg/kg) again,not terazosin.Results The concentration curves based on drug-time of experimental group and control group are presented by two-compartments model when using terazosin. The pharmacokinetic parameters were: t_1/2β(6.57±2.73) and (2.11±0.72)h; t_max(0.34±0.08) and (0.64±0.18)h; C_max (149.41±41.16) and (72.26±23.26)μg/g; CL(0.07±0.02) and (0.20±0.06)g/h; AUC_0–12 (608.02±226.82) and (253.67±91.68)μg·h·g^-1, respectively. There is significant difference about all parameters between experimental group and control group(P<0.01). When reaplaced by tamsulosin ,the concentration curves based on drug-time of experimental group and control group also are presented by two-compartments model. The pharmacokinetic parameters were: t_1/2β(5.91±1.81) and (2.87±0.98)h; t_max(1.08±0.22) and (1.00±0.13)h; C_max (30.02±4.57) and (22.05±3.36)μg/g; CL(0.23±0.04) and (0.51±0.02) g/h; AUC_0–12 (170.25±17.39) and (93.74±9.11)μg·h·g^-1, respectively, then there also is significant difference about every parameter between experimental group and control group(P<0.01), except t_max.Conclusionα1-adrenoceptor blocking drugs can significantly increase the concentration of antibacterial drugs in the tissue of prostatitis,prolong t_1/2β and decline Clearance,which make the time of effective concentration be prolonged.