Acquired immune deficiency syndrome protease inhibitors

Specific concomitant medications or consumptions (check specific statin package insert for warnings) fibrates (especially gemfibrozil, but other fibrates too), nicotinic acid (rarely), cyclosporine, azole antifungals such as itraconazole and ketoconazole, macrolide antibiotics such as erythromycin and clarithromycin, protease inhibitors used to treat Acquired Immune Deficiency Syndrome, nefazodone (antidepressant), verapamil, amiodarone, large quantities of grapefruit juice (usually more than 1 quart per day), and alcohol abuse (independently predisposes to myopathy)... 

The protease inhibitor cocktails referred to herein are not to be confused with the protease inhibitor cocktails that are used for therapy for patients who have Acquired Immune Deficiency Syndrome (AIDS). 

Solid Form Selection A drug can exist in multiple forms in the solid state. If the two forms have the same molecular structure but different crystal packing, then they are polymorphs. Pseudopolymorphs (or solvatomorphs) differ in the level of hydration/solvation between forms. Polymorphs and pseudopolymorphs in principle will have a different solubility, melting point, dissolution rate, etc. While less thermodynamically stable, polymorphs have higher solubilities they also have the potential to convert to the more thermodynamically stable form. This form conversion can lead to reduced solubility for the formulated product. One example is ritonavir, a protease inhibitor compound used to treat acquired immune deficiency syndrome (AIDS). Marketed by Abbott Labs as Norvir, this compound began production in a semisolid form and an oral liquid form. In July 1998, dissolution tests of several new batches of the product failed. The problem was traced to the appearance of a previously unknown polymorph (Form II) of the compound. This form is thermodynamically more stable than Form I and therefore is less soluble. In this case, the solubility is at least a factor of 2 below that of Form I.12 The discovery of this new polymorph ultimately led to a temporary withdrawal of the solid form of Norvir from the market and a search for a new formulation. 

The enzymes called proteases are necessary for the digestion of proteins. A newly proposed treatment for acquired immune deficiency syndrome (AIDS) involves the use of protease inhibitors, and as AIDS is an immunodeficiency disease, with cancer sometimes described in the same way, there may be a connection. (AIDS is by most accounts caused by the retrovirus HIV, and cancer may in some instances be traced to retroviruses.)... 

Many patients infected with the human immunodeficiency virus (HIV) that causes acquired immune deficiency syndrome (AIDS) are treated with a class of drugs called protease inhibitors. Before these drugs were developed in the early 1990s, HIV-infected individuals would die within a few years of diagnosis. Today, protease inhibitors, when given in combination with other drugs, can reduce HIV to undetectable levels and keep AIDS patients alive. 

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