Metabolic agents pravastatin

D Rifampin significantly reduces the plasma concentrations of the calcium channel blockers verapamil, diltiazem, and nifedipine. Diltiazem is a substrate of Gi P3A4 and rifampin is an inducer of CYP3A4. Rifampin does not interact with metoprolol, aspirin, pravastatin, or nitroglycerin. However, if the patient had been on another HMG-CoA reductase inhibitor such as atorvastatin, lova-statin, or simvastatin instead of pravastatin, rifampin would have reduced the plasma concentrations of these agents since they are also metabolized via CYP3A4. 

Meanwhile, the industry s R D race produced additional HMG-CoA reductase agents. Sankyo s second HMG-CoA reductase inhibitor, pravastatin, licensed to Bristol-Myers Squibb, entered phase III clinical trials in Japan at the same time lovastatin entered phase III clinical trials in the United States. In October 1990, 21 months after Bristol-Myers Squibb submitted the NDA on January 31, 1989, FDA s Endocrinologic and Metabolic Advisory Committee unanimously recommended pravastatin be approved On October 31, 1991, 3 years after approval in Japan, the FDA approved pravastatin with a 1C rating, a new molecular entity (NME) with little or no therapeutic gain over existing therapies. Bristol-Myers Squibb initially offered pravastatin at a direct price discount of 5 percent and a 10 percent discount to wholesalers of lovastatin. By 1993, pravastatin s sales are estimated to reach 500 million. 

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