Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis
Isoniazid is the most effective and widely used antituberculosis drug. The metabolism of isoniazid is noninducible and the primary metabolie route determining the rate at which isoniazid is eliminated from the body is acetylation. There are large differences between individuals in the rates at which...
Published in: | Clinical Pharmacology & Therapeutics |
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crwiley:10.1002/cpt1976195part2610 2024-06-02T08:06:10+00:00 Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis Ellard, G. A. 1976 http://dx.doi.org/10.1002/cpt1976195part2610 http://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcpt1976195part2610 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcpt1976195part2610 https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1002/cpt1976195part2610 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Clinical Pharmacology & Therapeutics volume 19, issue 5part2, page 610-625 ISSN 0009-9236 1532-6535 journal-article 1976 crwiley https://doi.org/10.1002/cpt1976195part2610 2024-05-03T10:47:03Z Isoniazid is the most effective and widely used antituberculosis drug. The metabolism of isoniazid is noninducible and the primary metabolie route determining the rate at which isoniazid is eliminated from the body is acetylation. There are large differences between individuals in the rates at which isoniazid and certain other hydrazides and some sulfonamides are acetylated. The acetylation of isoniazid is inherited in a simple Mendelian fashion, individuals being either slow, heterozygous rapid, or homozygous rapid acetylators . Improved methods of discriminating between the different phenotypes have recently been described that are also more convenient to use. The proportion of slow acetylators among Japanese and Eskimos is about 10%; among Chinese about 20%; among Caucasians, Negroes, and South Indians about 60%. The results of aseries of meticulously controlled clinical trials carried out in India, East Africa, Hong Kong, Singapore, Czechoslovakia, and Britain have shown the isoniazid acetylator status of tuberculosis patients treated with isoniazid‐containing regimens is of no prognostic significance when treatment is given on a daily basis. It may, however, be of significance when twice‐weekly regimens are employed, especially in circumstances in which only a short period of initial daily chemotherapy is given, and where the companion drug employed during the twice‐weekly continuation phase is relatively weak. The acetylator phenotype is, however, extremely important in once‐weekly treatment, rapid acetylators always having fared considerably worse than slow acetylators on all the regimens evaluated so far. Experimental studies of the action of isoniazid against Mycobacterium tuberculosis in vitro and in vivo have enabled these findings to be understood. Article in Journal/Newspaper eskimo* Wiley Online Library Clinical Pharmacology & Therapeutics 19 5part2 610 625 |
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English |
description |
Isoniazid is the most effective and widely used antituberculosis drug. The metabolism of isoniazid is noninducible and the primary metabolie route determining the rate at which isoniazid is eliminated from the body is acetylation. There are large differences between individuals in the rates at which isoniazid and certain other hydrazides and some sulfonamides are acetylated. The acetylation of isoniazid is inherited in a simple Mendelian fashion, individuals being either slow, heterozygous rapid, or homozygous rapid acetylators . Improved methods of discriminating between the different phenotypes have recently been described that are also more convenient to use. The proportion of slow acetylators among Japanese and Eskimos is about 10%; among Chinese about 20%; among Caucasians, Negroes, and South Indians about 60%. The results of aseries of meticulously controlled clinical trials carried out in India, East Africa, Hong Kong, Singapore, Czechoslovakia, and Britain have shown the isoniazid acetylator status of tuberculosis patients treated with isoniazid‐containing regimens is of no prognostic significance when treatment is given on a daily basis. It may, however, be of significance when twice‐weekly regimens are employed, especially in circumstances in which only a short period of initial daily chemotherapy is given, and where the companion drug employed during the twice‐weekly continuation phase is relatively weak. The acetylator phenotype is, however, extremely important in once‐weekly treatment, rapid acetylators always having fared considerably worse than slow acetylators on all the regimens evaluated so far. Experimental studies of the action of isoniazid against Mycobacterium tuberculosis in vitro and in vivo have enabled these findings to be understood. |
format |
Article in Journal/Newspaper |
author |
Ellard, G. A. |
spellingShingle |
Ellard, G. A. Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis |
author_facet |
Ellard, G. A. |
author_sort |
Ellard, G. A. |
title |
Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis |
title_short |
Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis |
title_full |
Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis |
title_fullStr |
Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis |
title_full_unstemmed |
Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis |
title_sort |
variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis |
publisher |
Wiley |
publishDate |
1976 |
url |
http://dx.doi.org/10.1002/cpt1976195part2610 http://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcpt1976195part2610 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcpt1976195part2610 https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1002/cpt1976195part2610 |
genre |
eskimo* |
genre_facet |
eskimo* |
op_source |
Clinical Pharmacology & Therapeutics volume 19, issue 5part2, page 610-625 ISSN 0009-9236 1532-6535 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/cpt1976195part2610 |
container_title |
Clinical Pharmacology & Therapeutics |
container_volume |
19 |
container_issue |
5part2 |
container_start_page |
610 |
op_container_end_page |
625 |
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1800751065242533888 |