{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:08:36Z","timestamp":1790633316383,"version":"4.1.0"},"reference-count":18,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The preferred antiretroviral regimen for young children previously exposed to non-nucleoside reverse transcriptase inhibitors is lopinavir\/ ritonavir plus two nucleoside reverse transcriptase inhibitors. Rifampicin-based antitubercular treatment reduces lopinavir concentrations. Adding extra ritonavir to lopinavir\/ ritonavir overcomes the effect of rifampicin, however this approach is not feasible in many settings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed an integrated population model describing lopinavir and ritonavir pharmacokinetics to predict lopinavir\/ritonavir (4:1) doses achieving target lopinavir exposures in children treated for tuberculosis. The model included data from 15 children given \u2018super-boosted\u2019 lopinavir (lopinavir\/ritonavir = 1:1) and 20 children given twice the standard dose of lopinavir\/ritonavir every 12 h during antitubercular treatment, and from children given standard lopinavir\/ritonavir doses every 12 h (39 without tuberculosis and 11 sampled again after antitubercular treatment).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A one-compartment model with first- order absorption and elimination best described the pharmacokinetics of lopinavir and a one-compartment model with transit absorption compartments described ritonavir pharmacokinetics. The dynamic influence of ritonavir concentration on lopinavir oral clearance was modelled as direct inhibition with an E\n                      <jats:sub>max<\/jats:sub>\n                      model. Antitubercular treatment reduced the oral bioavailability of lopinavir by 77% in children receiving twice usual lopinavir\/ritonavir doses and increased ritonavir clearance by 50%. Simulations predicted that respective 27, 21, 20 and 18 mg\/kg 8-hourly doses of lopinavir (in lopinavir\/ritonavir, 4:1) maintains lopinavir concentrations &gt;1 mg\/l in at least 95% of children weighing 3\u20135.9, 6\u20139.9, 10\u201313.9 and 14\u201319.9 kg.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The model describing the interactions between lopinavir, ritonavir and rifampicin in young children predicted feasible 8-hourly doses of lopinavir\/ ritonavir resulting in therapeutic lopinavir concentrations during antitubercular treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp1915","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T10:58:38Z","timestamp":1317207518000},"page":"25-33","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":24,"title":["Population Pharmacokinetics of Lopinavir and Ritonavir in Combination with Rifampicin-Based Antitubercular Treatment in HIV-Infected Children"],"prefix":"10.1177","volume":"17","author":[{"given":"Chao","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"McIlleron","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Ren","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Stefan","family":"van der Walt","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats O","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrika SH","family":"Simonsson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Denti","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2012,1,1]]},"reference":[{"key":"bibr1-IMP1915","unstructured":"World Health Organization. Antiretroviral therapy of HIV infection in infants and children: towards universal access: recommendations for a public health approach - 2010 revision. (Updated 15 March 2010. Accessed 15 March 2010). Available from http:\/\/www.who.int\/hiv\/pub\/paediatric\/paed-prelim-summary.pdf."},{"key":"bibr2-IMP1915","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.5.1553-1560.2004"},{"key":"bibr3-IMP1915","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3181642257"},{"key":"bibr4-IMP1915","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-010-0847-9"},{"key":"bibr5-IMP1915","doi-asserted-by":"crossref","unstructured":"Decloedt E.H., Maartens G., Smith P.J. The pharmacokinetics of lopinavir in South African HIV-infected volunteers receiving rifampicin with adjusted doses of lopinavir\/ritonavir.\n                      11th International Workshop on Clinical Pharmacology of HIV Therapy\n                      . 7\u20139 April 2010, Sorrento, Italy. Abstrct 47.","DOI":"10.1128\/AAC.01598-10"},{"key":"bibr6-IMP1915","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1757"},{"key":"bibr7-IMP1915","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2003.11.003"},{"key":"bibr8-IMP1915","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-2607(98)00067-4"},{"key":"bibr9-IMP1915","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-007-9066-0"},{"key":"bibr10-IMP1915","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.48.113006.094708"},{"key":"bibr11-IMP1915","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.24.25"},{"key":"bibr12-IMP1915","doi-asserted-by":"publisher","DOI":"10.1208\/ps040427"},{"key":"bibr13-IMP1915","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60916-8"},{"key":"bibr14-IMP1915","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2431-8-1"},{"key":"bibr15-IMP1915","first-page":"862","volume":"13","author":"Martinson N.A.","year":"2009","journal-title":"Int J Tuberc Lung Dis"},{"key":"bibr16-IMP1915","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00943-05"},{"key":"bibr17-IMP1915","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01374-08"},{"key":"bibr18-IMP1915","doi-asserted-by":"publisher","DOI":"10.2174\/157488407779422294"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP1915","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP1915","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:50:27Z","timestamp":1777380627000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP1915"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,1]]}},"alternative-id":["10.3851\/IMP1915"],"URL":"https:\/\/doi.org\/10.3851\/imp1915","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1]]}}}