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Rifamate

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Rifamate

CLINICAL PHARMACOLOGY

Rifampin

Rifampin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. This is the mechanism of action by which rifampin exerts its therapeutic effect. Rifampin cross-resistance has only been shown with other rifamycins.

In a study of 14 normal human adult males, peak blood levels of rifampin occurred 1 1/2 to 3 hours following oral administration of two RIFAMATE (rifampin and isoniazid) capsules. The peaks ranged from 6.9 to 14 mcg/mL with an average of 10 mcg/mL.

In normal subjects the T1/2 (biological half-life) of rifampin in blood is approximately 3 hours. Elimination occurs mainly through the bile and, to a much lesser extent, the urine.

Isoniazid

Isoniazid acts against actively growing tubercle bacilli.

After oral administration isoniazid produces peak blood levels within 1 to 2 hours which decline to 50% or less within 6 hours. It diffuses readily into all body fluids (cerebrospinal, pleural, and ascitic fluids), tissues, organs, and excreta (saliva, sputum, and feces). The drug also passes through the placental barrier and into milk in concentrations comparable to those in the plasma. From 50 to 70% of a dose of isoniazid is excreted in the urine in 24 hours.

Isoniazid is metabolized primarily by acetylation and dehydrazination. The rate of acetylation is genetically determined. Approximately 50% of Blacks and Caucasians are “slow inactivators”; the majority of Eskimos and Orientals are “rapid inactivators.”

The rate of acetylation does not significantly alter the effectiveness of isoniazid. However, slow acetylation may lead to higher blood levels of the drug, and thus an increase in toxic reactions.

Pyridoxine deficiency (B6) is sometimes observed in adults with high doses of isoniazid and is considered probably due to its competition with pyridoxal phosphate for the enzyme apotryptophanase.

Last reviewed on RxList: 2/24/2009
This monograph has been modified to include the generic and brand name in many instances.

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