Evaluation of the Pharmacokinetic Interaction between Candesartan Cilexetil and Felodipine

Abstract

The study was performed to evaluate the pharmacokinetic interaction of test formulation of candesartan 16 mg tablet and felodipine extended release 5 mg tablet together in a combination package, comparing with the fasting period intake of commercial formulations of both Atacand® 16 mg tablet and Splendil® extended release 5 mg tablet (Test formulation and reference formulation from AstraZeneca, Brazil) in 36 volunteers of both sexes. The study was conducted open with randomized three period crossover design and a one week wash out period. The candesartan and felodipine were analyzed by LC-MS-MS. The mean ratio of parameters C max and AUC 0-t and 90% confidence intervals of correspondents were calculated to determine the pharmacokinetic interaction. Geometric mean of candesartan exposure together in a combination package felodipine individual percent ratio was 102.51% AUC 0-t and 110.40% for C max . The 90% confidence intervals were 90.00 - 116.77% and 93.94 - 129.74%, respectively. Geometric mean of felodipine exposure together in a combination package candesartan individual percent ratio was 102.69% AUC 0-t and 96.17% for C max . The 90% confidence intervals were 89.46 - 117.88% and 82.07 - 112.69%, respectively. The major variable in this respect, AUC, was not signicantly affected by felodipine and candesartan with concomitant administration. The Cmax of candesartan was not signicantly affected by co-administration of felodipine. Based on these data and in presence in the market of isolated candersatana and felodipino formularizations used in combination in medical practice, it is concluded that there are no risk with concomitant administration between felodipine and candesartan.