Study on Pharmacokinetics of Capecitabine/Polyethylene Glycol 1000/Montmorillonite Compound in Rats in vivo / 中国药房

ABSTRACT

OBJECTIVE:To establish a method of determining the plasma concentration of capecitabine/polyethylene glycol 1000/montmorillonite (CAP/PEG1000/MMT) in rats’plasma for the study on pharmacokinetics of CAP compound in rats in vivo. METHODS:HPLC was adopted. The determination was performed on Kromasil C18 with mobile phase consisted of 0.1% glacial acetic acid-acetonitrile(73∶27),at the flow rate of 1.0 ml/min. The detection wavelength was 250 nm and column temperature was 40 ℃. The sample size was 10 μl. 18 Wistar rats were randomly divided into CAP group,CAP/MMT group(MMT as carrier)and CAP/PEG1000/MMT group(PEG1000/MMT as carrier)and ig given corresponding drugs,that equal to 200 mg/kg of CAP. Blood sample was respectively taken 15,30,60,90,120,180,240,300 and 360 min after the administration of drugs,and plasma was isolated and added with internal standard ferulic acid. The concentration of the drug in the plasma was determined by HPLC fol-lowing protein precipitation with methanol,based on which the pharmacokinetic parameters were calculated by 3p97 software. RE-SULTSThe linear range of CAP was 0.054 9-4.390 0 μg/ml (r=0.998 2) with the method recovery of 98.2%-102.1%(RSD=1.50%-3.29%, n=5) and absolute recovery of 76.2%-78.9%(RSD=2.29%-2.99%, n=5). In the above-mentioned three groups,t1/2 were(1.11±0.32),(1.57±0.32)and(1.62±0.10)h;cmax were(2.91±0.36),(0.91±0.23)and(0.91±0.14)μg/ml;AUC0-6 h were (8.70 ± 1.79),(3.76 ± 0.27) and (3.73 ± 0.25)μg·h/ml;and tmax were (0.97 ± 0.20),(1.55 ± 0.47) and (1.50 ± 0.07) h,respectively. There was no significant difference in the pharmacokinetic parameters between the CAP/MMT group and CAP/PEG1000/MMT group(P>0.05). CONCLUSIONS:The method is reliable and simple,and can be used for pharmacokinetic study of CAP/PEG1000/MMT in rats. MMT and PEG1000/MMT compound can prolong CAP acting time in the body.