Isoniazid Introduction

Control of tuberculosis, long one of the scourges of mankind, began with the introduction of effective antibacterial agents. Thus, this disease was treated initially with some small measure of success with various sulfa drugs the advent of the antibiotic, streptomycin, provided a major advance in antitubercular therapy, as did the subsequent discovery of isoniazid and its analogs. 

Isoniazid [eye soe NYE a zid], the hydrazide of isonicotinic acid, is a synthetic analog of pyridoxine. It is the most potent of the anti-tubercular drugs, but is never given as a single agent in the treatment of active tuberculosis. Its introduction revolutionized the treatment of tuberculosis. 

Isonicotinic acid hydrazide (isoniazid 275), a drug used in treating tuberculosis269, has been 1 -labelled264 by introduction of a [nC]cyano group at the 2-position of the pyridine ring of l-methoxy-4-methoxcarbonyl pyridinium methyl sulphate and subsequent treatment of the 1 -labelled methyl ester 276 with hydrazine hydrate. The reaction has been carried out on a solid support (silica gel) to yield methyl 2[11C]cyano-isonicotinate in 32.4+12% (EOB) yield. 275 was obtained in 10% (EOB), radiochemical... 

The authors noted that isoniazid-induced pellagra was first described in 1956, shortly after the introduction of isoniazid for the treatment of tuberculosis, but that subsequent reports have been very uncommon. 

A major advance in the treatment of tuberculosis was signaled by the introduction of the antibiotic rifampin into therapy. Clinical studies indicated that when rifampin is included in the regimen, particultu ly in combination with isoniazid... 

Thus far all mixtures considered have been static, in the sense that the probability model did not change as a function of covariate values. Recall that in the introduction, isoniazid acetylator polymorphism was used as an example to introduce the concept of mixture modeling utility. In that example it was stated that race was associated with how patients were partitioned between slow and fast acetylator status. So, given an isoniazid PK data set without acetylator genotype, but with race as a covariate, one might want to introduce race as a covariate in our mix block to help model the patients as either fast or slow acetylators. 

Isoniazid (INH) is one of the most effective first-line oral antituberculosis drugs and it was introduced to the treatment since its introduction in 1952 (Bernstein et al., 1952). It is usually consumed orally with a dosage of 5 mg/kg body weight (Hmama, 2013) (Figure 11.3). 

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