A comparative study of the metabolism and toxicity of isoniazid and isoniazone calcium pyruvate
1962; Churchill Livingstone; Volume: 43; Issue: 1 Linguagem: Inglês
10.1016/s0041-3879(62)80045-2
ISSN1878-6006
Autores Tópico(s)Tuberculosis Research and Epidemiology
ResumoA comparative study of the metabolism of isoniazid and isoniazone calcium pyruvate has been made in normal subjects and in patients with pulmonary tuberculosis. Absorption after oral ingestion of isoniazone calcium pyruvate was slower, but more prolonged than with isoniazid. Active serum concentrations in the region of peak absorption were lower with the pyruvate than with equivalent doses of isoniazid, but after the peak period, they tended to become higher. This effect occurred sooner with rapid than with slow inactivators. The excretion of free isoniazid and its hydrazone and acetyl derivatives was lower after the pyruvate, although the relative proportions of the three forms was the same with both drugs, indicating a similar metabolic pattern. Evidence from absorption and excretion studies as to whether isoniazone calcium pyruvate is hydrolysed prior to absorption is inconclusive. It is suggested that determinations of free isoniazid and hydrazone concentration in serum after oral ingestion of the drug might help to clarify this. Investigations with continuous treatment with the drugs gave no clear evidence that isoniazone calcium pyruvate has any less effect on pyridoxine excretion than isoniazid. This excretion was similar with both drugs, the increase above normal amounts being possibly more marked with slow inactivators than with rapid ones. The side effects experienced with the doses used were too severe to attempt to confirm this. It is possible that further experiments with lower doses and with divided doses might establish whether this difference between slow and rapid inactivators is true and might also reveal differences in the effect of isoniazone calcium pyruvate and isoniazid.
Referência(s)