The successful introduction of HMG-CoA reductase inhibitors for lipid lowering sparked intense competition in the field. pravastatin 4 (Figure 7) is made in a two-step fermentation process that first generates compactin with Penicillium citrinum, and after hydrolysis of the lactone, employs a biological hydroxylation with Streptomyces carbophilus to introduce the allylic 6-alcohol group regioselectively. Pravastatin has higher water solubility and provided several potential advantages over the more hydrophobic analogs, lovastatin and simvastatin. Unlike lovastatin and simvastatin, pravastatin sodium is administered as the sodium salt of the corresponding open-chain hydroxy-acid. The polar nature of pravastatin, however, limited its overall human absolute bioavailability to ~ 17%, presumably due to incomplete absorption and firstpass metabolism. However, pravastatin has been used to demonstrate the facilitated cellular uptake of compounds through organic anion transporter proteins. Compared to lovastatin and simvastatin, pravastatin has the added benefit of not being metabolized by CYP3A4 enzymes, thus reducing its potential for drug-drug interactions.62 Because of its polarity, much less pravastatin is protein-bound (~45%) compared to the high protein binding (>95%) observed for lovastatin and simvastatin. Pravastatin 4 was approved for human use in 1991.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

Get My Free Ebook

Post a comment