Ketoconazole pharmacokinetics

When ketoconazole is administered orally, it requires gastric acid for dissolution and is absorbed through the intestinal mucosa. Drugs that raise gastric pH, such as antacids, or that interfere with gastric acid secretion, such as H2-histamine– receptor blockers and proton-pump inhibitors, impair absorption. Administering acidifying agents, such as cola drinks, before taking the drug can improve absorption in patients with achlorhydria. Ketoconazole is extensively bound to plasma proteins. Although penetration into tissues is limited, it is effective in the treatment of histoplasmosis in lung, bone, skin, and soft tissues. The drug does not enter the CSF. Extensive metabolism occurs in the liver, and excretion is primarily through the bile. Levels of parent drug in the urine are too low to be eff ective against mycotic infections of the urinary tract.