The Interaction On Pharmacokinetics In Rats Between Matrine And Ceftiofur

As one of the main basic constituents of Sophora flavescens, also named in Chinese drugs as Ku-shen, (+)-Matrine exhibits a variety of pharmacological effects, antipyretic, antiulcer, anti-inflammatory, antiviral activity, antinociceptive effect and notable antitumor activities. According to Compendium of Materia Medica, Sophora root is cold by nature with bitter taste, entering three channels of heart, spleen and kidney with the function of relieving heat, depriving the evil wetness, puring fire for removing toxin and killing parasites to relieve itching. As a widely used medicinal herb it is usually prescribed for the treatment of diarrhea, gastrointestinal hemorrhage, eczema, and it possesses antipyretic, anti-inflammatory, analgesic effects.Matrine mainly distribution in kidney, liver, spleen, lung, brain, heart in the body. Ceftiofur is a third generation broad-spectrum cephalosporin with the broad spectrum bactericidal activity against a variety of gram positive, gram negative and anaerobic pathogens. Ceftiofur mainly distribution in kidney, lung, liver, fat, muscle. By studying vivo pharmacolinetic interaction of matrine and Ceftiofur hydrochloride in rats, explore the mechanism of the combination of Chinese with western medicine and provide reference for clinical use of drugs in Chinese and western medicine combination.The rats were divided into three groups:one group was administrated with matrine only, another group was administrated with Ceftiofur hydrochloride only and the other was administrated with matrine in combination with Ceftiofur hydrochloride. Plasma concentration of matrine and Ceftiofur hydrochloride were determined by HPLC, and the matrine was determined under the following conditions:column (Shim-pack VP-ODS,150Lx4.6,5μm); eluent (acetonitrile-0.02mol ammonium acetate buffer-triethylamine (30:70:0.04, v/v/v); flow rate was lmL/min and ultraviolet detection wavelength was set at 220nm; column temperature 40℃; aliquot injected 20μL.The Chromatographic conditions of Ceftiofur hydrochloride:column (Shim-pack VP-ODS,150Lx4.6,5μm); eluent (acetonitrile-0.1% trifluoroacetic acid (30:70, v/v); flow rate was 1mL/min and ultraviolet detection wavelength was set at 266nm; column temperature 40℃; aliquot injected 20μL. The pharmacokinetic parameters were calculated from the plasma concentration-time data using the DAS 2.1.1 software program.To investigate the effect of Ceftiofur hydrochloride on the pharmacokinetics of matrine in rats. The main pharmacokinetic parameters for the control group were Cmax=21.1139 mg-L-1, Tmax=0.75 h, t1/2a=1.34 h, t1/2β=3.509 h,AUC0～t=90.984 mg-h-L-1 and AUC0～8=100.346 mg-h-L-1, and the data for the combination group were Cmax=11.707 mg-L-1,Tmax=0.917 h, t1/2α=1.598 h, t4/2β=3.247 h, AUC0～t=53.28 mg-h-L-1 and AUC0-8=60.035 mg·h-L-1. The effect of Ceftiofur hydrochloride on pharmacokinetics of matrine in rats showed that the plasma concentration of matrine and bioavailability in combination group were significantly lower than those of the control group. In combination group, matrine had a higher clearance and volume of distribution in the central compartments, as well as a lower volume of distribution in the peripheral compartments. The main pharmacokinetic parameters found for Ceftiofur hydrochloride single drug group were as follows:Cmax=24.311 mg·L-1, Tmax=0.278 h, t1/2=0.371 h, AUC0～t=26.847 mg·h·L-1, AUC0～8=29.021 mg·h·L-1; while the drugs combination group of matrine were Cmax=39.437 mg-L-1, Tmax=0.472 h, t1/2=0.777 h, AUC0～t=42.724 mg·h·L-1,AUC0～8=45.779 mg··h·L-1. Compare with single drug group was administrated with Ceftiofur hydrochloride, the Ceftiofur hydrochloride plasma concentration of combination administration group is higher, as the same as the absolute bioavailability. The absorption rate of Ceftiofur hydrochloride was decreased, while the half-life was significantly longer. The clearance was decreased.In combination group, the maximum concentrations of matrine in heart, liver, spleen, lung, kidney, brain was 20.02μg/g,58.21μg/g,103.68μg/g,37.29μg/g,167.00μg/g,37.00,μg/g. It was demonstrated that matrine of combination group had a higher volume of distribution in the central compartments, as well as a higher concentration of distribution in heart, liver, spleen, lung, kidney, brain. In control group, the tissue distribution of matrine in rats was kidney>liver>spleen>lung>brain>heart, while the combination group was kidney>spleen>liver>lung>brain>heart.The Writhing Test showed that the antinociceptive potencies of combination group was higher than control group was administrated with matrine. The study demonstrated that matrine of combination group had a higher volume of distribution in brain.