[Bioavailability of isoniazid in healthy volunteers--fast and slow INH acetylators].
The major pathway for INH metabolism is acetylation of acetyloisoniazid by a noninducible hepatic enzyme N-acetyltransferase. Examples of drugs acetylated by this enzymatic system are: isoniazid, sulphadimidine, hydralazine, dapson and sulphapiridine. The rate of acetylation is constant in any individual but varies in different patients. People are characterized as rapid or slow acetylators with slow acetylation inherited as an autosomal recessive type. Heterozygotes have intermediate acetylation rate. Methods for determining acetylator phenotype have been proposed by many authors, but the many of them need instrumentation such as photometers, centrifuges, chromatographs etc. For estimating of INH acetylator phenotype we have developed a sensitive and rapid biological method with Mycobacterium aurum REB as a standard strain. The linearity, precision and accuracy of the method have been evaluated. The minimum detectable concentration of INH was determined to be 0.5 mcg/ml. The test should be completed within 5 days. The described method for determination of INH in human plasma is sensitive and reproducible and allowed to provide pharmacokinetic studies in fast (8 healthy volunteers) and slow (12 healthy volunteers) acetylators. The results have shown that all compared parameters are significantly different in both groups of acetylators.
Augustynowicz-Kopeć
Ewa
E
Zakładu Mikrobiologii IGiChP w Warszawie.
Zwolska
Zofia
Z
Niemirowska-Mikulska
Hanna
H
D000107:Acetylation; D000328:Adult; D000995:Antitubercular Agents / Q000097:blood / Q000493:pharmacokinetics*; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D001682:Biological Availability; D006801:Humans; D007538:Isoniazid / Q000097:blood / Q000493:pharmacokinetics*; D009161:Mycobacterium / Q000378:metabolism; D010641:Phenotype; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors
D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; D007538:Isoniazid