{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:47:38Z","timestamp":1783385258965,"version":"3.54.6"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T00:00:00Z","timestamp":1583107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009252","name":"Science for Life Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009252","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:p>Tuberculosis is the most common cause of death in HIV\u2010infected patients. Isoniazid is used as a first\u2010line drug to treat tuberculosis infection. However, variability in isoniazid pharmacokinetics can result in hepatotoxicity or treatment failure. Determination of clinical factors affecting isoniazid pharmacokinetics and metabolic pathways in HIV co\u2010infected patients is therefore critical. Plasma levels of isoniazid, acetyl\u2010isoniazid, and isonicotinic acid from 63 patients co\u2010infected with tuberculosis and HIV were analyzed by liquid chromatography with tandem mass spectrometry followed by nonlinear mixed\u2010effects modeling. Patients were genotyped to determine acetylator status. Patients were either on concomitant efavirenz\u2010based antiretroviral therapy or HIV treatment na\u00efve. Clearances of isoniazid were 1.3\u2010fold and 2.3\u2010fold higher in intermediate and rapid acetylators, respectively, compared with slow acetylators. Patients on concomitant efavirenz\u2010based antiretroviral therapy had 64% and 80% higher population predicted clearances of acetyl\u2010isoniazid and isonicotinic acid, respectively, compared with patients who were HIV treatment na\u00efve. Both sex and CD4 cell count affected the bioavailability of isoniazid. Variability in isoniazid exposure could be reduced by dose adaptions based on acetylator type and sex in addition to the currently used weight bands. A novel dosing strategy that has the potential to reduce isoniazid\u2010related toxicity and treatment failure is presented.<\/jats:p>","DOI":"10.1002\/cpt.1806","type":"journal-article","created":{"date-parts":[[2020,2,4]],"date-time":"2020-02-04T14:34:12Z","timestamp":1580826852000},"page":"73-80","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Model\u2010Based Assessment of Variability in Isoniazid Pharmacokinetics and Metabolism in Patients Co\u2010Infected With Tuberculosis and HIV: Implications for a Novel Dosing Strategy"],"prefix":"10.1111","volume":"108","author":[{"given":"Jesper","family":"Sundell","sequence":"first","affiliation":[{"name":"Unit for Pharmacokinetics and Drug Metabolism Department of Pharmacology Sahlgrenska Academy at University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile","family":"Bienvenu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy School of Medicine and Pharmacy University of Rwanda Kigali Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Janz\u00e9n","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Pharmacokinetics, Early Cardiovascular, Renal and Metabolism BioPharmaceuticals R&amp;D AstraZeneca Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Birgersson","sequence":"additional","affiliation":[{"name":"Unit for Pharmacokinetics and Drug Metabolism Department of Pharmacology Sahlgrenska Academy at University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"\u00c4bel\u00f6","sequence":"additional","affiliation":[{"name":"Unit for Pharmacokinetics and Drug Metabolism Department of Pharmacology Sahlgrenska Academy at University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ashton","sequence":"additional","affiliation":[{"name":"Unit for Pharmacokinetics and Drug Metabolism Department of Pharmacology Sahlgrenska Academy at University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,2]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01086149"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01063121"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2016.07.014"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920007782798216"},{"key":"e_1_2_10_5_1","first-page":"51","article-title":"Hydrazine\u2013a possible cause of isoniazid\u2013induced hepatic necrosis","volume":"23","author":"Woo J.","year":"1992","journal-title":"J. Med."},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(84)90063-5"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2008.01.002"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01244-15"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02379-13"},{"key":"e_1_2_10_10_1","first-page":"139","article-title":"Effect of efavirenz\u2010based antiretroviral therapy and high\u2010dose rifampicin on the pharmacokinetics of isoniazid and acetyl\u2010isoniazid","volume":"74","author":"Chirehwa M.T.","year":"2019","journal-title":"J. Antimicrobial Chemotherapy"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2011.03940.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05526-11"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01345-13"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-014-0222-8"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-007-0305-5"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.4236\/pp.2015.611055"},{"key":"e_1_2_10_17_1","unstructured":"World Health Organization.Consolidated guidelines on general HIV care and the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach<https:\/\/www.who.int\/hiv\/pub\/guidelines\/arv2013\/en\/> (2013)."},{"key":"e_1_2_10_18_1","first-page":"237","article-title":"Frequencies of single nucleotide polymorphisms in cytochrome P450 genes (CYP1A2, 2A6, 2B6, 3A4 and 3A5) in a Rwandan population: difference to other African populations","volume":"11","author":"Bienvenu E.","year":"2013","journal-title":"Curr. Pharm. Personal. Med."},{"key":"e_1_2_10_19_1","article-title":"SNP genotyping using the Sequenom MassARRAY iPLEX platform","volume":"60","author":"Gabriel S.","year":"2009","journal-title":"Curr. Protocol. Human Genet."},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp121"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2018.10.027"},{"key":"e_1_2_10_22_1","volume-title":"NONMEM Users Guides","author":"Beal S.","year":"1989"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3182\/20120711-3-BE-2027.00381"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-016-9487-8"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00637563"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.02.017"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-009-0777-6"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.4.1170-1177.2006"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1445-5994.2003.00390.x"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/106002809603000901"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.11.4473-4475.2004"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3283319908"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.031393"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ155"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02532-14"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32814e6b08"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2014.03.003"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-012-1429-9"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S87131"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1403"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpt.1806","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1806","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.1806","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1806","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:37:22Z","timestamp":1699364242000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.1806"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,2]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1002\/cpt.1806"],"URL":"https:\/\/doi.org\/10.1002\/cpt.1806","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,2]]},"assertion":[{"value":"2019-11-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}