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Rifampin-induced Release of Hydrazine From Isoniazid. A Possible Cause of Hepatitis During Treatment of Tuberculosis With Regimens Containing Isoniazid and Rifampin

Rifampin-induced Release of Hydrazine From Isoniazid. A Possible Cause of Hepatitis During Treatment of Tuberculosis With Regimens Containing Isoniazid and Rifampin

G R Sarma, C Immanuel, S Kailasam, A S Narayana, P Venkatesan

Am Rev Respir Dis. 1986 Jun;133(6):1072-5.

PMID: 3717759

Abstract:

The effect of daily administration of rifampin on the direct conversion of isoniazid to isonicotinic acid and hydrazine by isoniazid hydrolase was investigated in 6 slow and 8 rapid acetylators of isoniazid. The proportion of isoniazid metabolized through this direct pathway during the first 6 h was estimated from the ratio of total isonicotinic acid formed to acetylisoniazid in urine after administration of isoniazid or acetylisoniazid. In slow acetylators, this proportion was approximately 3% when isoniazid alone was administered and approximately 6% during the maximal phase of induction caused by the daily administration of rifampin in addition to isoniazid (p less than 0.001); in rapid acetylators, the proportions were considerably less (less than 1 and 2.5%, respectively), suggesting that isoniazid hydrolase was induced by rifampin. The increased formation of hydrazine, a known hepatotoxic agent in animals, could explain the substantially higher frequency of the occurrence of hepatitis in slow than in rapid acetylators among tuberculous patients treated with daily rifampin and isoniazid.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP54853-A	Isoniazid		54-85-3	Price

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