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Editor's Correspondence
April 9, 2001

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

Arch Intern Med. 2001;161(7):1012-1013. doi:

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.

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