Food effect on pharmacokinetic parameters of Losartan & its active metabolite

To evaluate the food effect on pharmacokinetic parameters of losartan and its active metabolite pharmacokinetics data of reference product 100mg tablet of two bio-equivalence studies were combined and analyzed. Fifty two and fifty nine healthy male subjects participated respectively in fasting and nonfasting study. Subjects received 100mg losartan tablet after overnight fasting condition of 12 hours for fasting study and after 30 minutes of high fat breakfast for non fasting study. Blood samples were collected prior to dosing and at regular time intervals as per predefine sampling time point over a period of 48 hours. Plasma samples were analysed for concentration of losartan and its metabolite using validated liquid chromatograph mass spectroscopy (LC-MS/MS) technique. The maximum plasma concentration (Cmax) of losartan and its metabolite were decreased up to 16% and 17% respectively. The area under curve (AUC) increased about 14% for losartan and decreased about 4% for metabolite whereas Time to attain maximum concentration (Tmax) were delayed about 107 % (from 1.36 h to 2.82 h) and 59 % (from 3.058 to 4.864 hours) for losartan and metabolite respectively. Elimination constant (Kel) for losartan was delay 18 % for fasting study and for metabolite Kel was delay 4 % for fasting study. For the log transformed data of losartan, food effect was found for pharmacokinetics parameters Cmax, AUCt (area under curve up to last measurable time point) and AUCi (area under curve up to infinity time). While in case of metabolite food effect was found for Cmax lack of food effect was observed on AUCt and AUCi of clinically active metabolite which conformed food had not a significant effect on the efficacy of the losartan.