{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:31:40Z","timestamp":1791113500858,"version":"4.1.0"},"reference-count":35,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"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":[[2011,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alternatives to the available stavudine-containing paediatric fixed-dose combination (FDC) tablets are rapidly needed due to concerns regarding the cumulative toxicity of long-term stavudine exposure. We report the bioavailability and short-term safety of a novel paediatric FDC tablet of zidovudine (ZDV)\/lamivudine (3TC)\/nevirapine (NVP; 30\/15\/28 mg) in HIV-infected children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this Phase I\/II open-label pharmacokinetic study, 42 children weighing 6\u201330 kg treated with NVP-based HAART for \u22654 weeks were randomized to receive the FDC tablets (GPO-VIR Z30) or the liquid formulations. Dosing was weight-based. Intensive 12-h blood sampling was performed after 2 weeks; subjects then crossed-over to the alternate formulation at equal doses and sampling repeated 2 weeks later. Pharmacokinetic parameters were determined by non-compartmental analysis. Buccal-swab samples were collected for cytochrome P450 ( CYP)2B6 polymorphism analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>With the FDC tablet, the geometric mean (90% CI) area under the curve (AUC) for ZDV, 3TC and NVP was 1.58 (1.49-1.68), 7.78 (7.38-8.19) and 68.88 (62.13-76.36) \u03bcg\u2022h\/ml, respectively. Rules for NVP therapeutic inadequacy were defined a priori, and despite lower NVP exposure with the tablet ( P &lt;0.001), the levels remained therapeutically adequate. ZDV AUC was similar between formulations. 3TC exposure was significantly higher with the tablet but comparable to historical data in adults and children taking branded tablets. While receiving the tablet, NVP AUC in children with CYP2B 516 GG (45%), GT (45%) and TT (10%) genotypes were 67.0, 74.5 and 106.4 \u03bcg\u2022h\/ml, respectively ( P =0.04).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Disparities in drug exposure between formulations were observed; however, the FDC tablet delivered therapeutically adequate exposures of each drug and could well play an important role in simplifying antiretroviral treatment for children.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp1931","type":"journal-article","created":{"date-parts":[[2011,10,24]],"date-time":"2011-10-24T09:08:01Z","timestamp":1319447281000},"page":"1287-1295","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":35,"title":["Pharmacokinetics and Safety of a New Paediatric Fixed-Dose Combination of Zidovudine\/Lamivudine\/Nevirapine in HIV-Infected Children"],"prefix":"10.1177","volume":"16","author":[{"name":"the IMPAACT P1069 Team","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kulkanya","family":"Chokephaibulkit","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim R","family":"Cressey","sequence":"additional","affiliation":[{"name":"Program for HIV Prevention and Treatment (PHPT), Division of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand"},{"name":"Harvard School of Public Health, Boston, MA, USA"},{"name":"Institut de Recherche pour le D\u00e9veloppement (IRD), Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund","family":"Capparelli","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pharmacy and Drug Discovery, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virat","family":"Sirisanthana","sequence":"additional","affiliation":[{"name":"Research Institute for Health Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petronella","family":"Muresan","sequence":"additional","affiliation":[{"name":"Harvard School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchat","family":"Hongsiriwon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Chonburi Hospital, Chonburi, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaiwat","family":"Ngampiyaskul","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Prapokklao Hospital, Chantaburi, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanin","family":"Limwongse","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orasri","family":"Wittawatmongkol","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Aurpibul","sequence":"additional","affiliation":[{"name":"Research Institute for Health Sciences, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bill","family":"Kabat","sequence":"additional","affiliation":[{"name":"Children's Memorial Hospital, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MariPat","family":"Toye","sequence":"additional","affiliation":[{"name":"Baystate Medical Center, Springfield, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Elizabeth","family":"Smith","sequence":"additional","affiliation":[{"name":"Pediatric Medicine Branch, Division of AIDS, National Institute of Allergy and Infectious Diseases, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achara","family":"Eksaengsri","sequence":"additional","affiliation":[{"name":"Thai Government Pharmaceutical Organization, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"McIntosh","sequence":"additional","affiliation":[{"name":"Harvard School of Public Health, Boston, MA, USA"},{"name":"Division of Infectious Diseases, Children's Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Yogev","sequence":"additional","affiliation":[{"name":"Children's Memorial Hospital, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2011,11,1]]},"reference":[{"key":"bibr1-IMP1931","unstructured":"World Health Organization, UNAIDS. Estimated number of children (<15 years) newly infected with HIV, 2007. (Updated December 2007. Accessed 23 September 2010.) Available at: http:\/\/data.unaids.org\/pub\/EPISlides\/2007\/071118_epicore2007_slides_en.pdf."},{"key":"bibr2-IMP1931","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000183625.97170.59"},{"key":"bibr3-IMP1931","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e31818dd72b"},{"key":"bibr4-IMP1931","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e318125720a"},{"key":"bibr5-IMP1931","unstructured":"World Health Organization. Summary statement on WHO recommendations on ARV medicines for treating and preventing HIV infections in younger children. (Updated 30 November 2006. Accessed 23 September 2010.) Available from http:\/\/www.who.int\/hiv\/mediacentre\/news63\/en\/."},{"key":"bibr6-IMP1931","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3282f4a208"},{"key":"bibr7-IMP1931","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e3181e2189d"},{"key":"bibr8-IMP1931","volume-title":"Preferred antiretroviral medicines for treating and preventing HIV infection in younger children: report of the WHO Paediatric Antiretroviral Working Group.","author":"World Health Organization.","year":"2008"},{"key":"bibr9-IMP1931","unstructured":"World Health Organization. Rapid advice: antiretroviral therapy for HIV infection in adults and adolescents: November 2009 version. November 2009 (Updated 23 February 2010. Accessed 23 September 2010.) Available from http:\/\/www.who.int\/hiv\/pub\/arv\/rapid_advice_art.pdf."},{"key":"bibr10-IMP1931","doi-asserted-by":"publisher","DOI":"10.2478\/abm-2010-0065"},{"key":"bibr11-IMP1931","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1293.2008.00689.x"},{"key":"bibr12-IMP1931","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3282ef9695"},{"key":"bibr13-IMP1931","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-200306000-00023"},{"key":"bibr14-IMP1931","doi-asserted-by":"publisher","DOI":"10.1097\/01.ftd.0000211817.58052.b8"},{"key":"bibr15-IMP1931","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2004.031708"},{"key":"bibr16-IMP1931","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200106150-00003"},{"key":"bibr17-IMP1931","doi-asserted-by":"publisher","DOI":"10.1089\/08892220260190290"},{"key":"bibr18-IMP1931","doi-asserted-by":"publisher","DOI":"10.1592\/phco.21.5.424.34497"},{"key":"bibr19-IMP1931","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.7.1708"},{"key":"bibr20-IMP1931","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199911120-00006"},{"key":"bibr21-IMP1931","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100118"},{"key":"bibr22-IMP1931","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2652-13-S4-P176"},{"key":"bibr23-IMP1931","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3280117ca0"},{"key":"bibr24-IMP1931","doi-asserted-by":"publisher","DOI":"10.1097\/01.qai.0000199098.95967.ab"},{"key":"bibr25-IMP1931","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140090-00005"},{"key":"bibr26-IMP1931","unstructured":"European Medicines Agency (EMEA). Annex I: summary of product characteristics. Viramune 200 mg tablets. (Updated 6 August 2010. Accessed 23 September 2010.) Available from http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_-_Product_Information\/human\/000183\/WC500051481.pdf."},{"key":"bibr27-IMP1931","unstructured":"Clinical pharmacology review: NDA: 20-636 SE5 027 & 20-933 SE5 017. (Updated 8 September 2008. Accessed 24 February 2011.) Available from http:\/\/www.fda.gov\/downloads\/Drugs\/DevelopmentApprovalProcess\/DevelopmentResources\/ucm072778.pdf."},{"key":"bibr28-IMP1931","unstructured":"Mulenga V., Fillekes Q., Kabamba D. Pharmacokinetics of nevirapine in 3- to 6-kg, HIV-infected infants taking pediatric fixed-dose combination tablets.\n                      16th Conference on Retroviruses and Opportunistic Infections.\n                      8\u201310 February 2009, Montreal, QC, Canada. Abstract 881."},{"key":"bibr29-IMP1931","unstructured":"Mosha L.B., Musoke P., Parsons T. Nevirapine concentrations in HIV-infected Ugandan children on adult fixed-dose combination tablet ART, with and without rifampicin-based treatment for active\n                      M. Tuberculosis\n                      infection.\n                      16th Conference on Retroviruses and Opportunistic Infections.\n                      8\u201310 February 2009, Montreal, QC, Canada. Abstract 909."},{"key":"bibr30-IMP1931","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/174.4.713"},{"key":"bibr31-IMP1931","unstructured":"WHO paediatric antiretroviral working group. Preferred antiretroviral medicines for treating and preventing HIV infection in younger children. (Updated 20 January 2008. Accessed 23 September 2010.) Available from http:\/\/www.who.int\/hiv\/pub\/paediatric\/antiretroviral\/en\/index.html."},{"key":"bibr32-IMP1931","unstructured":"Capparelli E., Kabamba D., Cressey T.R., Burger D.M. Nevirapine exposure with WHO pediatric weight band dosing \u2013 enhanced therapeutic concentrations predicted based on extensive international pharmacokinetic experience.\n                      15th Conference on Retroviruses and Opportunistic Infections.\n                      3\u20136 February 2008, Boston, MA, USA. Abstract 576."},{"key":"bibr33-IMP1931","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)07276-8"},{"key":"bibr34-IMP1931","first-page":"2391","volume":"18","author":"Haas D.W.","year":"2004","journal-title":"AIDS"},{"key":"bibr35-IMP1931","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1177\/135965350901400316","volume":"14","author":"Puthanakit T.","year":"2009","journal-title":"Antivir Ther"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP1931","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP1931","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:50:26Z","timestamp":1777380626000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP1931"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11]]},"references-count":35,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2011,11]]}},"alternative-id":["10.3851\/IMP1931"],"URL":"https:\/\/doi.org\/10.3851\/imp1931","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,11]]}}}