{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T05:56:19Z","timestamp":1768283779683,"version":"3.49.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The aim of this study was to examine the relationships between\n            <jats:italic>N<\/jats:italic>\n            -acetyltransferase genotypes, pharmacokinetics, and tolerability of granular slow-release\n            <jats:italic>para<\/jats:italic>\n            -aminosalicylic acid (GSR-PAS) in tuberculosis patients. The study was a randomized, two-period, open-label, crossover design wherein each patient received 4 g GSR-PAS twice daily or 8 g once daily alternately. The PAS concentration-time profiles were modeled by a one-compartment disposition model with three transit compartments in series to describe its absorption. Patients'\n            <jats:italic>NAT1<\/jats:italic>\n            and\n            <jats:italic>NAT2<\/jats:italic>\n            genotypes were determined by sequencing and restriction enzyme analysis, respectively. The number of daily vomits was modeled by a Poisson probability mass function. Comparisons of other tolerability measures by regimens, gender, and genotypes were evaluated by a linear mixed-effects model. The covariate effects associated with efavirenz, gender, and\n            <jats:italic>NAT1*3<\/jats:italic>\n            ,\n            <jats:italic>NAT1*14<\/jats:italic>\n            , and\n            <jats:italic>NAT2*5<\/jats:italic>\n            alleles corresponded to 25, 37, \u221217, \u221248, and \u221227% changes, respectively, in oral clearance of PAS. The\n            <jats:italic>NAT1*10<\/jats:italic>\n            allele did not influence drug clearance. The time above the MIC of 1 mg\/liter was significantly different between the two regimens but not influenced by the\n            <jats:italic>NAT1<\/jats:italic>\n            or\n            <jats:italic>NAT2<\/jats:italic>\n            genotypes. The occurrence and intensity of intolerance differed little between regimens. Four grams of GSR-PAS twice daily but not 8 g once daily ensured concentrations exceeding the MIC (1 mg\/liter) throughout the dosing interval; PAS intolerance was not related to maximum PAS concentrations over the doses studied and was not more frequent after once-daily dosing. We confirm that the slow phenotype conferred by the\n            <jats:italic>NAT1*14<\/jats:italic>\n            and\n            <jats:italic>NAT1*3<\/jats:italic>\n            alleles resulted in higher PAS exposure but found no evidence of increased activity of the\n            <jats:italic>NAT1*10<\/jats:italic>\n            allele.\n          <\/jats:p>","DOI":"10.1128\/aac.04049-14","type":"journal-article","created":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T02:32:06Z","timestamp":1431397926000},"page":"4129-4138","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["<i>N<\/i>\n            -Acetyltransferase Genotypes and the Pharmacokinetics and Tolerability of\n            <i>para<\/i>\n            -Aminosalicylic Acid in Patients with Drug-Resistant Pulmonary Tuberculosis"],"prefix":"10.1128","volume":"59","author":[{"given":"Sherwin K. B.","family":"Sy","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lizanne","family":"de Kock","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas H.","family":"Diacon","sequence":"additional","affiliation":[{"name":"Task Applied Science, Bellville, Cape Town, South Africa"},{"name":"Division of Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cedric J.","family":"Werely","sequence":"additional","affiliation":[{"name":"MRC Centre for Tuberculosis Research, DST-NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiming","family":"Xia","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Rosenkranz","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lize","family":"van der Merwe","sequence":"additional","affiliation":[{"name":"MRC Centre for Tuberculosis Research, DST-NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"},{"name":"Department of Statistics, Faculty of Natural Sciences, University of the Western Cape, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter R.","family":"Donald","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(46)91185-3"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5138.1610"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.159.3.9807131"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/j.1875-9114.1994.tb02787.x","article-title":"Pharmacokinetic evaluation of para-aminosalicylic acid granules","volume":"14","author":"Peloquin CA","year":"1994","unstructured":"Peloquin CA, Henshaw TL, Huitt GA, Berning SE, Nitta AT, James GT. 1994. Pharmacokinetic evaluation of para-aminosalicylic acid granules. Pharmacotherapy 14:40\u201346.","journal-title":"Pharmacotherapy"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1A088"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/tropej\/fms053"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-014-0172-7"},{"key":"e_1_3_2_9_2","volume-title":"Guidelines for the programmatic management of drug-resistant tuberculosis. Emergency update 2008. WHO\/HTM\/TB\/2008.402","author":"World Health Organization","year":"2000","unstructured":"World Health Organization. 20008. Guidelines for the programmatic management of drug-resistant tuberculosis. Emergency update 2008. WHO\/HTM\/TB\/2008.402. World Health Organization, Geneva, Switzerland. http:\/\/www.who.int\/tb\/challenges\/mdr\/programmatic_guidelines_for_mdrtb\/en\/."},{"key":"e_1_3_2_10_2","first-page":"13","volume-title":"Drug susceptibility in the chemotherapy of mycobacterial infections","author":"Heifets LB","year":"1991","unstructured":"Heifets LB. 1991. Antituberculosis drugs: antimicrobial activity in vitro, p 13\u201358. In Heifets LB (ed), Drug susceptibility in the chemotherapy of mycobacterial infections. CRC Press, Boca Raton, FL."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01197-08"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-1304-6_8"},{"key":"e_1_3_2_13_2","first-page":"169","article-title":"The role of the metabolism of p-aminosalicylic acid (PAS) in the treatment of tuberculosis. 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