Study on the Pharmacokinetic Interaction between Lercanidipine and Doxofylline in Rats
OBJECTIVE To investigate the pharmacokinetic interaction of the lercanidipinecombinewith doxo-fylline in rats.METHODS Rats wererandomly divided into three groups,which were administrated with lercanidip-ine,doxofylline,lecardipine+doxofyll ine,respectively.Blood was collected from orbitat different time points,and plasma was obtained by centrifugation.A HPLC method was established for simultaneous determination of lercanidip-ine and doxofyllineconcentrations,the average blood concentration-time curve was drawn and the pharmacokinetic pa-rameters were analyzed by DAS 3.2 software.RESULTS The main pharmacokinetic parameters of lercanidipinein alone and in combination were as follows:AUC0-∞:(2389.80±579.60)and(1402.64±166.18)μg/(h·mL);MRT0-∞:(5.91±0.95)and(4.97±0.31)h;t1/2:(2.78±0.76)and(2.10±0.78)h;Tmax:(3.00±1.10)and(3.33±1.03)h;CL:(6.60±1.66)and(10.82±1.26)L/(h·kg);Cmax:(388.44±70.64)and(259.20±51.16)ng·mL-1.The pharmacokinetic parameters of doxofylline alone and in combination were as follows:AUC0-∞:(41.30±2.26)and(17.71±2.40)mg/(h·mL);MRT0-∞:(2.09±0.16)and(2.34±0.34)h;t1/2:(1.51±0.28)and(1.44±0.33)h;Tmax:(0.50±0.00)and(0.50±0.00)h;CL:(1.21±0.07)and(2.86±0.34)L/(h·kg);Cmax:(15.46±0.84)and(9.18±0.68)mg·mL-1.CONCLUSION Compared with single use,the AUC0-∞,Cmax and K valuesof lercanidipinewere significantly decreased and CL was significantly increased after combi-nation(P＜0.01).The AUC0-∞、Cmax of doxofyllinewere significantly decreased,while CL was significantly increased(P＜0.01).The combination of the two drugs leads to delayed absorption and accelerated elimination,so the combi-nation of the two drugs is not recommended.
万方数据
维普
