We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Editor's Correspondence |

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

Michael B. Bottorff, PharmD; Philip Hansten, PharmD
Arch Intern Med. 2001;161(7):1012-1013. doi:.
Text Size: A A A
Published online


In reply

We appreciate the opportunity to respond to the insightful comments by Dr Vormfelde regarding pharmacokinetics and drug interactions with the statins. With regard to cerivastatin, both the CYP3A4 and CYP2C8 pathways contribute to its metabolism and elimination. Since the submission of the original manuscript, the effects of CYP3A4 inhibition by itraconazole on cerivastatin pharmacokinetics revealed an insignificant increase in cerivastatin acid area under the curve (AUC) of 15%; however, an increase in cerivastatin lactone AUC of 2.6-fold was observed.1 The increase in AUC is more pronounced with coadministration of itraconazole and other CYP3A4-metabolized statins, leading to the conclusion that the CYP3A4 pathway is less important than the CYP2C8 pathway for cerivastatin elimination. Although few drugs are known substrates or inhibitors in the CYP2C8 pathway, unknown or future CYP2C8 inhibitors may have a pronounced effect on cerivastatin pharmacokinetics and increase the likelihood for myopathy. Tranilast, an inhibitor of growth factors released after angioplasty,2 is a known CYP2C9 inhibitor and has recently been identified as a potent CYP2C8 inhibitor as well, causing myopathy in patients receiving cerivastatin (David J. Kazierad, PharmD, oral communication, SmithKline Beecham Pharmaceuticals, Philadelphia, Pa, July 23, 2000). Also, the concurrent use of cerivastatin and gemfibrozil has also been associated with an increased risk of myopathy,3 and this combination is now contraindicated and reflected in the current cerivastatin package insert. Thus, cerivastatin may be less susceptible than some statins to drug interactions involving CYP3A4; however, important interactions with both CYP2C8 inhibition and gemfibrozil (mechanisms unknown) must be remembered.

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

First Page Preview

View Large
First page PDF preview





April 9, 2001
Michael B. Bottorff, PharmD; Philip Hansten, PharmD
Arch Intern Med. 2001;161(7):1012-1013. doi:.
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles

Users' Guides to the Medical Literature
The Biological Agent

Users' Guides to the Medical Literature
Is There Potentially Compelling Evidence for a Class Effect?