A case study of single-pill combination therapy: the ezetimibe/simvastatin combination for treatment of hyperlipidemia.
In recent years, combination therapy has received growing popularity as a powerful therapeutic tactic for the treatment of diseases. The justifications and benefits of combination therapy are far-reaching, including but not limited to addressing unmet medical needs such as cancer, malaria, and HIV/AIDS, improved clinical efficacy and safety with reduced dosage of a single medication, understanding the underlying science of the disease, alleviating pharmaco-economic impacts, and better drug life-cycle management. Using the ezetimibe/simvastatin combination therapy as a case study, a comprehensive overview of the successful discovery and development of the single-pill combination, Vytorin, is presented in this review. A cursory introduction to combination therapy and the rationale for the ezetimibe/simvastatin combination for the treatment of hyperlipidemia provides an instructive entry point. The discovery and mode of action of simvastatin and ezetimibe monotherapies set the scene for a detailed discussion on the discovery and development of Vytorin, with emphasis on bioequivalency studies, clinical efficacy and safety profile studies, and the economic consequences of the single-pill combination therapy. Large-scale outcome clinical trials are also discussed to demonstrate the long-term effects of Vytorin.
Merck Research Laboratory, Rahway, NJ 07065 (USA). xianhai.huang@merck.com.
Xianhai
X
Huang
David Y-K
DY
Chen
D000818:Animals; D001384:Azetidines / Q000191:economics / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004338:Drug Combinations; D055808:Drug Discovery / Q000379:methods; D000069499:Ezetimibe, Simvastatin Drug Combination; D006331:Heart Diseases / Q000150:complications; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000191:economics / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D019821:Simvastatin / Q000191:economics / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D001384:Azetidines; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D000960:Hypolipidemic Agents; D019821:Simvastatin