Compositions with reduced hepatotoxicity

Abstract

Pharmaceutical compositions of hepatotoxic compounds are provided in which the hepatotoxicity of the compounds is mitigated by including quantities of nicotinamide and methionine in the composition. Folic acid also can be included to further mitigate the hepatotoxic effects. The hepatotoxic compounds can include acetaminophen, methotrexate, atorvastatin, simvastatin, niacin, flucanozole, divalproex sodium, and valproic acid.

Description

BACKGROUND OF THE INVENTION [0001] This invention relates to compositions of pharmaceutical compounds having hepatotoxicity, in which compositions the hepatotoxicity is mitigated. More particularly, this invention relates to compositions of hepatotoxic compounds such as acetaminophen, methotrexate, statin drugs, niacin, divalproex sodium, valproic acid or fluconazole, each of which is known to have hepatotoxic properties, in which compositions the hepatotoxicity of the compound is mitigated. [0002] Acetaminophen is the active metabolite of phenacetin, a drug whose use extends back to the 1880's. Although acetaminophen was first used as an analgesic and antipyretic in 1893, it did not achieve widespread use until after 1949. For many years, acetaminophen was used as a second-line choice to aspirin as an analgesic / antipyretic, but the elucidation of the relationship between aspirin use and Reye's Syndrome and the recognition of aspirin's propensity to produce gastrointestinal bleeding...

AI Technical Summary

Problems solved by technology

While acetaminophen is usually well tolerated, its use can be accompanied by a very serious adverse effect—potentially fatal hepatic necrosis.

While methotrexate administration is associated with various other side effects, severe and sometimes fatal liver toxicity is a significant limiting factor in its therapeutic usefulness.

In spite of their widespread use, liver toxicity is a significant problem, and patients with a history of old or active hepatitis must avoid these drugs even if they could benefit from their cholesterol lowering actions.

Niacin (also known as nicotinic acid or vitamin B3), another agent frequently employed as a cholesterol lowering agent, is also associated with a high incidence of liver toxicity.