Clinical pharmacokinetics of clofazimine. A review.

Clofazimine is useful in the treatment of Hansen's disease (leprosy) and some dermatological disorders, and is currently being used in drug regimens for patients with human immunodeficiency viral infections who are also infected with Mycobacterium avium complex. After an oral dose, absorption is variable, but when given in an oil-wax suspension is approximately 70%. Administration with food appears to increase the peak plasma drug concentration and reduce the time to peak level. Data on the volume of distribution and percentage or type of protein binding are not available; however, the drug undergoes extensive tissue distribution. Clofazimine does not cross the blood-brain barrier, but does cross the placenta, and is found in human breast milk. To date 3 urinary metabolites have been identified in man, but their biological activity is unknown. A substantial portion of the unchanged drug is excreted in faeces. The elimination half-life is variable, with values as long as 70 days being quoted in the literature. Frequently reported side effects of clofazimine are hyperpigmentation of the skin and conjunctiva, and abdominal pain. These resolve upon cessation of therapy. Biochemical and haematological adverse effects have been reported, but are generally not clinically relevant. Pharmacokinetic drug interactions of potential clinical significance have been observed with dapsone, oestrogen, rifampicin and vitamin A.