1. To elucidate any potential species differences, the in vitro metabolism of pitavastatin and its lactone was studied with hepatic and renal microsomes from rats, dogs, rabbits, monkeys and humans. 2. With the addition of UDP-glucuronic acid to hepatic microsomes, pitavastatin lactone was identified as the main metabolite in several animals, including humans. 3. Metabolic clearances of pitavastatin and its lactone in monkey hepatic microsome were much greater than in humans. 4. M4, a metabolite of pitavastatin with a 3-dehydroxy structure, was converted to its lactone form in monkey hepatic microsomes in the presence of UDP-glucuronic acid as well as to pitavastatin. These results implied that lactonization is a common pathway for drugs such as 5-hydroxy pentanoic acid derivatives. 5. The acid forms were metabolized to their lactone forms because of their structural characteristics. 6. UDP-glucuronosyltransferase is the key enzyme responsible for the lactonization of pitavastatin, and overall metabolism is different compared with humans owing to the extensive oxidative metabolism of pitavastatin and its lactone in monkey.