INH 代謝型と尿中 INH 代謝物排泄ならびに Sulfa 剤代謝との関係
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1. The biologically active plasma levels of INH after the oral administration of 4 mg/kg of INH were determined by means of the Vertical Diffusion method, and classified on the following criteria:<BR>6 hour level<BR>Rapid Inactivator (R):<BR>Equal to or less than O.15 mcg/ml<BR>Intermediate Inactivator (I):<BR>Between O.15 and 0.8 mcg/ml<BR>Slow Inactivator (S):<BR>Equal to or more than 0.8 mcg/ml<BR>2. The amount of free isoniazid excreted i n urine measured by the Hughes Method increases in the order of R, I and S. (Table 1 & 2, and Fig.1, 2, 3 & 4) If we express three groups of metabolites excreted in 6 hour urine in percentage, the amounts of free INH and hydrazone are the largest in slow inactivators, showing that slow inactivators can not acetylate INH to the full extent and are obliged to compensate the insufficient acetylation by the increased formation of hydrazone. (Fig.5)<BR>3. The simultaneous determination of the biologically active INH in blood plasma and the free INH in urine reveals that there is a direct but not very close correlation between them. (Table 3, and Fig.6 & 7) The average values of the percentages of the free INH in 6 hour urine for rapid, intermediate and slow inactivators are 9.08, 10.92 and 18.56 respectively. But it does not seem possible to have the same classification of rapid, intermediate and slow inactivators on the basis of urine analysis as on the 6 hour blood level.<BR>4. The influence of the increased doses of INH upon the biologically active INH blood levels in rapid inactivators in the case of Japanese is less remarkable than in the Caucasians, but more marked than in the Esquimos. (Fig.8 & 9) If the test doses are raised, both free and acetyl INH in urine increase to some extent, but the increase of hydrazone is the most remarkable, and if we express the relative amount of respective metabolites in percentage, free INH remains almost unchanged, acetyle INH decreases and hydrozone increases markedly. (Fig.10)Hydrozone seems to play a role of buffer also under these circumstances.<BR>5. The relationship between the concentration of the free sulfonamide in blood plasma 9 hours after the oral dose of 1g of sulfisoxazole measured by means of Bratton-Marshalls technique and the biologically active blood level of INH 4 hours after the administration of INH is demonstrated to a certain extent. (Table 3 & 4, and Fig.11, 12, 13& 14)