{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T15:39:05Z","timestamp":1766158745354,"version":"3.40.5"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206379\/Z\/17\/Z"],"award-info":[{"award-number":["206379\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001713","name":"European and Developing Countries Clinical Trials Partnership","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Abacavir is part of WHO\u2010recommended regimens to treat HIV in children under 15\u2009years of age. In a pooled analysis across four studies, we describe abacavir population pharmacokinetics to investigate the influence of age, concomitant medications, malnutrition and formulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 230 HIV\u2010infected African children were included, with median (range) age of 2.1 (0.1\u201312.8) years and weight of 9.8 (2.5\u201330.0) kg. The population pharmacokinetics of abacavir was described using nonlinear mixed\u2010effects modelling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Abacavir pharmacokinetics was best described by a two\u2010compartment model with first\u2010order elimination, and absorption described by transit compartments. Clearance was predicted around 54% of its mature value at birth and 90% at 10\u00a0months. The estimated typical clearance at steady state was 10.7\u00a0L\/h in a child weighing 9.8\u00a0kg co\u2010treated with lopinavir\/ritonavir, and was 12% higher in children receiving efavirenz. During coadministration of rifampicin\u2010based antituberculosis treatment and super\u2010boosted lopinavir in a 1:1 ratio with ritonavir, abacavir exposure decreased by 29.4%. Malnourished children living with HIV had higher abacavir exposure initially, but this effect waned with nutritional rehabilitation. An additional 18.4% reduction in clearance after the first abacavir dose was described, suggesting induction of clearance with time on lopinavir\/ritonavir\u2010based therapy. Finally, absorption of the fixed dose combination tablet was 24% slower than the abacavir liquid formulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this pooled analysis we found that children on lopinavir\/ritonavir or efavirenz had similar abacavir exposures, while concomitant TB treatment and super\u2010boosted lopinavir gave significantly reduced abacavir concentrations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14984","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T15:13:13Z","timestamp":1626275593000},"page":"403-415","source":"Crossref","is-referenced-by-count":3,"title":["Abacavir pharmacokinetics in African children living with HIV: A pooled analysis describing the effects of age, malnutrition and common concomitant medications"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2488-7390","authenticated-orcid":false,"given":"Tjokosela","family":"Tikiso","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine University of Cape Town  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"McIlleron","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine University of Cape Town  Cape Town South Africa"},{"name":"Wellcome Centre for Infectious Diseases Research in Africa (CIDRI\u2010Africa), Institute of Infectious Disease and Molecular Medicine University of Cape Town  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7279-2818","authenticated-orcid":false,"given":"David","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Radboud University Medical Centre  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Gibb","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit at University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"Rabie","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health and Family Centre for Research with Ubuntu (FAM\u2010CRU) Stellenbosch University and Tygerberg Children's Hospital  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice","family":"Lee","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative  Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Lallemant","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative  Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark F.","family":"Cotton","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health and Family Centre for Research with Ubuntu (FAM\u2010CRU) Stellenbosch University and Tygerberg Children's Hospital  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3082-9234","authenticated-orcid":false,"given":"Moherndran","family":"Archary","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health at King Edward VIII Hospital affiliated to the Nelson R Mandela School of Medicine University of KwaZulu\u2010Natal  South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5972-3711","authenticated-orcid":false,"given":"Stefanie","family":"Hennig","sequence":"additional","affiliation":[{"name":"Certara, Inc.  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