Safety of Statins (Hydroxymethyl Glutaryl Coenzyme A Reductase Inhibitors): Different Mechanisms of Metabolism and Drug Transport May Have Clinical Relevance

I read with interest the article by Bottorff and Hansten¹ on the long-term safety of hepatic hydroxymethyl glutaryl coenzyme A reductase inhibitors, which appeared in the August 2000 issue of the ARCHIVES. However, there are some inconsistencies that I would like to comment on.

1. In contrast to statements made by Bottorff and Hansten, cerivastatin, unlike other statins, has a dual metabolic pathway.² The major pathway seems to be via CYP2C8, with a significant contribution by CYP3A4. Clinically, this leads to such a low interaction profile with CYP3A4 inhibitors that cerivastatin does not require or necessitate dose reductions when used along with inhibitors of CYP3A4.^2,3 The number of clinical important interactors at CYP2C8 is small compared with those at CYP3A4.