Comparison on Pharmacokinetics of Atorvastatin Calcium Tablets in Human and Beagle Dogs

A LC-MS/MS method was established for the determination of atorvastatin(1) and its active metabolites,ortho-hydroxy-atorvastatin(2) and para-hydroxy-atorvastatin(3),in human and Beagle dog plasma after oral administration of atorvastatin calcium tablets.The pharmacokinetic parameters of 1,2 and 3 were calculated and compared.The results indicated that the parent drug 1 was the main format circulated in human bodies,and the active metabolite 3 was not detected.While in Beagle dogs,the active metabolite 2 was the main format,with co-existence of parent drug 1 accounting for 30%as well as metabolite 3 accounting for 5%.The half life time of 1 in human bodies was about three times as long as that in Beagle dogs,while its clearance in human bodies was about 65%of that in Beagle dogs.In conclusion,there were significant pharmacokinetic differences of 1 between human and Beagle dogs.Both metabolism velocity and extent of parent drug in Beagle dogs were significantly higher than those in human bodies.