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肺結核患者의 Isoniazid 代謝와 그 臨床的 效果에 關한 硏究

Isoniazid Metabolism in Patients with Pulmonary Tuberculosis and its Clinical Implications

최신의학 1963년 6권 7호 p.99 ~ 106
이혜수,
소속 상세정보
이혜수 (  ) - 제18육군병원

Abstract


Most of the orally administered isoniazid is metabolically converted to derivatives that posses virtually no antimicrobial activity. The most abundant of these metabolites is the acetyl derivatives 1--4>.
Individual patients vary widely in the degree to which they metabolically alter isoniazid. Despite this wide variation among different persons, an individual demonstrates the same general type of metabolic pattern on repeated testing 2.4.6.7% Mitchell and his co-workers divided patients into three groups on serum concentrations of biologically active drugs six hours after the oral administration of a single dose, 4 mg/ml, of isoniazid. Persons whose serum isoniazid concentrations are 0.2 mcg/ml or less are regarded as rapid inactivators; those with a serum concentrations of 0.8 mcg/ml or more are regarded as slow inactivators; those with a serum concentration of 0.4 mcg/ml arc regarded as intermediate inactivators 8 10).
Some clinical observations indicate that the patients who belong to rapid inactivators demonstrate sub-optimal response to isoniazid therapy and the patients who belong to slow inactivators are likely to achieve optimal response to isoniazid therapy s `a ~;´~>. Some observers, however, do not agree with the above opinions 36-18).
The two hour serum isoniazid concentration is invariably greater than the six hour level and is considered to represent an approximation of a peal: level J´´"´!´- It is evident that the better therapeutic results were associated with the higher peak scrum concentrations rather than with difference in the period minimal inhibitory concentrations were maintained "-
Therefore, the author has devided the isoniazid metabolic patterns into three groups; "rapid metabolizers" and slow metabolizers with a group of "intermediate metabolizers" between these two extremes according to the peak levers. Persons whose scrum isoniazid concentrations :u-e 0.8mcg/ml or less two hours after a test dose, 4mg%kg, of isoniazid are classified as rapid metabolizers; those with a scrum concentrations of 3.2mcg/ml or more are classified as slow motabolizeres; those with a serum concentration of 1.6 mcg/ml are classified as intermediate metabolizers.
The purpose of this study is to compare the clinical efficacies between cases with rapid metabolizers and cases with intermediate and slow metabolizers.
Result
1. Among X31 cases of pulmonary tuberculosis, 118 were rapid nwtabolizer:149 were intermediate an the remaining 54 cases were slow metabolizers.
2. In rapid metabolizers the daily does of irs,niiazid of 41nc,%1,9 v;a:, apperard to bo in:,u;Tlcient arld 8 mg/kg or more of isoniazid was necessary to obtain optimal response.
2. There were significant differences in the isoniazid metabolic patterns betwecrr NI tchch´s classification and author´s classification. The author´s classification of the isoniazid metabolic patterns was more closely corelated with clinical results.

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