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Doubled doses of lopinavir\/ritonavir compensate for the effect of rifampicin in adults, but fail to provide adequate lopinavir concentrations in young children on rifampicin\u2010based antituberculosis therapy. The objective of this study was to develop a population pharmacokinetic model describing the pharmacokinetic differences of lopinavir and ritonavir, with and without rifampicin, between children and adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An integrated population pharmacokinetic model developed in <jats:sc>nonmem<\/jats:sc> 7 was used to describe the pharmacokinetics of lopinavir and ritonavir in 21 <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> infected adults, 39 <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> infected children and 35 <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> infected children with tuberculosis, who were established on lopinavir\/ritonavir\u2010based antiretroviral therapy with and without rifampicin\u2010containing antituberculosis therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The bioavailability of lopinavir was reduced by 25% in adults whereas children on antituberculosis treatment experienced a 59% reduction, an effect that was moderated by the dose of ritonavir. Conversely, rifampicin increased oral clearance of both lopinavir and ritonavir to a lesser extent in children than in adults. Rifampicin therapy in administered doses increased <jats:styled-content style=\"fixed-case\">CL<\/jats:styled-content> of lopinavir by 58% in adults and 48% in children, and <jats:styled-content style=\"fixed-case\">CL<\/jats:styled-content> of ritonavir by 34% and 22% for adults and children, respectively. In children, the absorption half\u2010life of lopinavir and the mean transit time of ritonavir were lengthened, compared with those in adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The model characterized important differences between adults and children in the effect of rifampicin on the pharmacokinetics of lopinavir and ritonavir. As adult studies cannot reliably predict their magnitude in children, drug\u2013drug interactions should be evaluated in paediatric patient populations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12101","type":"journal-article","created":{"date-parts":[[2013,2,25]],"date-time":"2013-02-25T10:46:10Z","timestamp":1361789170000},"page":"741-751","source":"Crossref","is-referenced-by-count":15,"title":["Model\u2010based evaluation of the pharmacokinetic differences between adults and children for lopinavir and ritonavir in combination with rifampicin"],"prefix":"10.1111","volume":"76","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":"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"}]},{"given":"Eric H.","family":"Decloedt","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":"Mats O.","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences Uppsala University  Uppsala Sweden"}],"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"}]}],"member":"311","published-online":{"date-parts":[[2013,10,21]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Antiretroval Therapy for HIV Infection in Infants and Children: Towards Universal Access Recommendations for A Public Health Approach","author":"World Health Organization","year":"2010"},{"key":"e_1_2_9_3_1","volume-title":"Antiretroviral Therapy for HIV Infection in Adults and Adolescents \u2013 Recommendations for A Public Health Approach","author":"World Health Organization","year":"2010"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01598-10"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.5.1553-1560.2004"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1757"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3181642257"},{"key":"e_1_2_9_8_1","volume-title":"NONMEM Users Guides","author":"Beal S","year":"2008"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2003.11.003"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-2607(98)00067-4"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2011.04154.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1915"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.48.113006.094708"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113249"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.177"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.3.2.147"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/1539-6924.00295"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1086\/380795"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1055-3290(06)60137-4"},{"key":"e_1_2_9_20_1","unstructured":"AwnlW ChluYL ZhuT BraunN KleinC HeuserR BreitenbachJ MorrisJ DoanT BrunS HannaG.Significantly reduced food effect and pharmacokinetic variability with a novel lopinavir\/ritonavir tablet formulation.Third IAS conference on HIV pathogenesis and treatment. 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