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The Role of Metabolism—Monograph for Physicians

Michael Bottorff, PharmD; Philip Hansten, PharmD

Arch Intern Med. 2000;160:2273-2280.

	Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.

INTRODUCTION

The hepatic hydroxymethyl glutaryl coenzyme A reductase inhibitors (HMGs) have an excellent safety profile.^1-2 Each of the 6 members of this therapeutic class (lovastatin,³ simvastatin,⁴ pravastatin,⁵ fluvastatin,⁶ atorvastatin,⁷ and cerivastatin⁸) has a low risk (<1%) of adverse drug reactions (ADRs). Nevertheless, some differences in safety have emerged within this category. The physicochemical properties of the HMGs may have important clinical implications. There are metabolic differences among the 6 available HMGs that may translate into significant differences in long-term safety.

Two of the ways that physicians help to ensure the safety of their patients is by prescribing agents that minimize the risk of ADRs, especially those caused by drug-drug interactions, and by counseling patients about potential drug interactions associated with HMG therapy. Therefore, it is important for physicians to understand the differences among the HMGs with regard to safety. The objectives of this review . . . [Full Text of this Article]

PHYSICOCHEMICAL AND PHARMACOKINETIC DIFFERENCES

THE ROLE OF THE CYP450 SYSTEM IN DRUG METABOLISM

OVERVIEW OF HMG DRUG METABOLISM: FOCUS ON CYP450 ISOFORMS

METABOLIC DIFFERENCES AMONG THE HMGs: CLINICAL DATA

Drug Interaction Studies

Effects of Diltiazem on Lovastatin and Pravastatin

Effects of Itraconazole on Atorvastatin, Lovastatin, Simvastatin, and Pravastatin

Clinical Implications of Drug Interaction Studies

Drug Interactions and Rhabdomyolysis

Case Reports of Myopathy or Rhabdomyolysis

Rhabdomyolysis With Lovastatin and Erythromycin

Myopathy With Lovastatin and Diltiazem

Rhabdomyolysis With Simvastatin and Itraconazole

Myositis and Rhabdomyolysis With Simvastatin and Nefazodone

Rhabdomyolysis With Simvastatin and Mibefradil

Rhabdomyolysis With Pravastatin

CLINICAL IMPLICATIONS OF DRUG METABOLISM DURING HMG THERAPY: GUIDELINES FOR HMG THERAPY

CONCLUSIONS

From the Departments of Pharmacy, University of Cincinnati, Cincinnati, Ohio (Dr Bottorff), and the School of Pharmacy, University of Washington, Seattle (Dr Hansten).

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