Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis

摘要: Isoniazid is the most effective and widely used antituberculosis drug. The metabolism of isoniazid noninducible primary metabolic route determining rate at which eliminated from body acetylation. There are large diffrences between individuals in rates certain other hydrazides some sulfonamides acetylated. acetylation inherited a simple Mendelian fashion, being either slow, heterozygous rapid, or homozygous rapid acetylators. Improved methods discriminating different phenotypes have recently been described that also more convenient to use. proportion slow acetylators among Japanese Eskimos about 10%; Chinese 20%; Caucasians, Negroes, South Indians 60%. results series meticulously controlled clinical trials carried out India, East Africa, Hong Kong, Singapore, Czechoslovakia, Britain shown acetylator status tuberculosis patients treated with isoniazid-containing regimens no prognostic significance when treatment given on daily basis. It may, however, be twice-weekly employed, especially circumstances only short period initial chemotherapy given, where companion drug employed during continuation phase relatively weak. phenotype is, extremely important once-weekly treatment, always having fared considerably worse than all evaluated so far. Experimental studies action against Mycobacterium vitro vivo enabled these findings understood.