@article{Tikiso2021,
abstract = {Aims Abacavir is part of WHO-recommended regimens to treat HIV in children under 15 years 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. Methods A total of 230 HIV-infected African children were included, with median (range) age of 2.1 (0.1-12.8) years and weight of 9.8 (2.5-30.0) kg. The population pharmacokinetics of abacavir was described using nonlinear mixed-effects modelling. Results Abacavir pharmacokinetics was best described by a two-compartment model with first-order elimination, and absorption described by transit compartments. Clearance was predicted around 54{\%} of its mature value at birth and 90{\%} at 10 months. The estimated typical clearance at steady state was 10.7 L/h in a child weighing 9.8 kg co-treated with lopinavir/ritonavir, and was 12{\%} higher in children receiving efavirenz. During co-administration of rifampicin-based antituberculosis treatment and super-boosted 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-based therapy. Finally, absorption of the fixed dose combination tablet was 24{\%} slower than the abacavir liquid formulation. Conclusion In this pooled analysis we found that children on lopinavir/ritonavir or efavirenz had similar abacavir exposures, while concomitant TB treatment and super-boosted lopinavir gave significantly reduced abacavir concentrations.},
annote = {https://doi.org/10.1111/bcp.14984},
author = {Tikiso, Tjokosela and McIlleron, Helen and Burger, David and Gibb, Diana and Rabie, Helena and Lee, Janice and Lallemant, Marc and Cotton, Mark F and Archary, Moherndran and Hennig, Stefanie and Denti, Paolo},
doi = {https://doi.org/10.1111/bcp.14984},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Tikiso et al. - 2021 - Abacavir pharmacokinetics in African children living with HIV a pooled analysis describing the effects of age, ma.pdf:pdf},
issn = {0306-5251},
journal = {British Journal of Clinical Pharmacology},
keywords = {Abacavir,Children,Efavirenz,Lopinavir,Malnutrition,Population pharmacokinetics,Rifampicin,fund{\_}not{\_}ack,original},
mendeley-tags = {fund{\_}not{\_}ack,original},
month = {jul},
number = {2},
pages = {403--415},
pmid = {34260082},
publisher = {John Wiley {\&} Sons, Ltd},
title = {{Abacavir pharmacokinetics in African children living with HIV: a pooled analysis describing the effects of age, malnutrition and common concomitant medications}},
url = {https://doi.org/10.1111/bcp.14984},
volume = {88},
year = {2021}
}

{"_id":"RLTaRAzZqEL7Bs3df","bibbaseid":"tikiso-mcilleron-burger-gibb-rabie-lee-lallemant-cotton-etal-abacavirpharmacokineticsinafricanchildrenlivingwithhivapooledanalysisdescribingtheeffectsofagemalnutritionandcommonconcomitantmedications-2021","author_short":["Tikiso, T.","McIlleron, H.","Burger, D.","Gibb, D.","Rabie, H.","Lee, J.","Lallemant, M.","Cotton, M. F","Archary, M.","Hennig, S.","Denti, P."],"bibdata":{"bibtype":"article","type":"article","abstract":"Aims Abacavir is part of WHO-recommended regimens to treat HIV in children under 15 years 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. Methods A total of 230 HIV-infected African children were included, with median (range) age of 2.1 (0.1-12.8) years and weight of 9.8 (2.5-30.0) kg. The population pharmacokinetics of abacavir was described using nonlinear mixed-effects modelling. Results Abacavir pharmacokinetics was best described by a two-compartment model with first-order elimination, and absorption described by transit compartments. Clearance was predicted around 54% of its mature value at birth and 90% at 10 months. The estimated typical clearance at steady state was 10.7 L/h in a child weighing 9.8 kg co-treated with lopinavir/ritonavir, and was 12% higher in children receiving efavirenz. During co-administration of rifampicin-based antituberculosis treatment and super-boosted 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-based therapy. Finally, absorption of the fixed dose combination tablet was 24% slower than the abacavir liquid formulation. Conclusion In this pooled analysis we found that children on lopinavir/ritonavir or efavirenz had similar abacavir exposures, while concomitant TB treatment and super-boosted lopinavir gave significantly reduced abacavir concentrations.","annote":"https://doi.org/10.1111/bcp.14984","author":[{"propositions":[],"lastnames":["Tikiso"],"firstnames":["Tjokosela"],"suffixes":[]},{"propositions":[],"lastnames":["McIlleron"],"firstnames":["Helen"],"suffixes":[]},{"propositions":[],"lastnames":["Burger"],"firstnames":["David"],"suffixes":[]},{"propositions":[],"lastnames":["Gibb"],"firstnames":["Diana"],"suffixes":[]},{"propositions":[],"lastnames":["Rabie"],"firstnames":["Helena"],"suffixes":[]},{"propositions":[],"lastnames":["Lee"],"firstnames":["Janice"],"suffixes":[]},{"propositions":[],"lastnames":["Lallemant"],"firstnames":["Marc"],"suffixes":[]},{"propositions":[],"lastnames":["Cotton"],"firstnames":["Mark","F"],"suffixes":[]},{"propositions":[],"lastnames":["Archary"],"firstnames":["Moherndran"],"suffixes":[]},{"propositions":[],"lastnames":["Hennig"],"firstnames":["Stefanie"],"suffixes":[]},{"propositions":[],"lastnames":["Denti"],"firstnames":["Paolo"],"suffixes":[]}],"doi":"https://doi.org/10.1111/bcp.14984","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Tikiso et al. - 2021 - Abacavir pharmacokinetics in African children living with HIV a pooled analysis describing the effects of age, ma.pdf:pdf","issn":"0306-5251","journal":"British Journal of Clinical Pharmacology","keywords":"Abacavir,Children,Efavirenz,Lopinavir,Malnutrition,Population pharmacokinetics,Rifampicin,fund_not_ack,original","mendeley-tags":"fund_not_ack,original","month":"jul","number":"2","pages":"403–415","pmid":"34260082","publisher":"John Wiley & Sons, Ltd","title":"Abacavir pharmacokinetics in African children living with HIV: a pooled analysis describing the effects of age, malnutrition and common concomitant medications","url":"https://doi.org/10.1111/bcp.14984","volume":"88","year":"2021","bibtex":"@article{Tikiso2021,\r\nabstract = {Aims Abacavir is part of WHO-recommended regimens to treat HIV in children under 15 years 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. Methods A total of 230 HIV-infected African children were included, with median (range) age of 2.1 (0.1-12.8) years and weight of 9.8 (2.5-30.0) kg. The population pharmacokinetics of abacavir was described using nonlinear mixed-effects modelling. Results Abacavir pharmacokinetics was best described by a two-compartment model with first-order elimination, and absorption described by transit compartments. Clearance was predicted around 54{\\%} of its mature value at birth and 90{\\%} at 10 months. The estimated typical clearance at steady state was 10.7 L/h in a child weighing 9.8 kg co-treated with lopinavir/ritonavir, and was 12{\\%} higher in children receiving efavirenz. During co-administration of rifampicin-based antituberculosis treatment and super-boosted 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-based therapy. Finally, absorption of the fixed dose combination tablet was 24{\\%} slower than the abacavir liquid formulation. Conclusion In this pooled analysis we found that children on lopinavir/ritonavir or efavirenz had similar abacavir exposures, while concomitant TB treatment and super-boosted lopinavir gave significantly reduced abacavir concentrations.},\r\nannote = {https://doi.org/10.1111/bcp.14984},\r\nauthor = {Tikiso, Tjokosela and McIlleron, Helen and Burger, David and Gibb, Diana and Rabie, Helena and Lee, Janice and Lallemant, Marc and Cotton, Mark F and Archary, Moherndran and Hennig, Stefanie and Denti, Paolo},\r\ndoi = {https://doi.org/10.1111/bcp.14984},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Tikiso et al. - 2021 - Abacavir pharmacokinetics in African children living with HIV a pooled analysis describing the effects of age, ma.pdf:pdf},\r\nissn = {0306-5251},\r\njournal = {British Journal of Clinical Pharmacology},\r\nkeywords = {Abacavir,Children,Efavirenz,Lopinavir,Malnutrition,Population pharmacokinetics,Rifampicin,fund{\\_}not{\\_}ack,original},\r\nmendeley-tags = {fund{\\_}not{\\_}ack,original},\r\nmonth = {jul},\r\nnumber = {2},\r\npages = {403--415},\r\npmid = {34260082},\r\npublisher = {John Wiley {\\&} Sons, Ltd},\r\ntitle = {{Abacavir pharmacokinetics in African children living with HIV: a pooled analysis describing the effects of age, malnutrition and common concomitant medications}},\r\nurl = {https://doi.org/10.1111/bcp.14984},\r\nvolume = {88},\r\nyear = {2021}\r\n}\r\n","author_short":["Tikiso, T.","McIlleron, H.","Burger, D.","Gibb, D.","Rabie, H.","Lee, J.","Lallemant, M.","Cotton, M. F","Archary, M.","Hennig, S.","Denti, P."],"key":"Tikiso2021","id":"Tikiso2021","bibbaseid":"tikiso-mcilleron-burger-gibb-rabie-lee-lallemant-cotton-etal-abacavirpharmacokineticsinafricanchildrenlivingwithhivapooledanalysisdescribingtheeffectsofagemalnutritionandcommonconcomitantmedications-2021","role":"author","urls":{"Paper":"https://doi.org/10.1111/bcp.14984"},"keyword":["Abacavir","Children","Efavirenz","Lopinavir","Malnutrition","Population pharmacokinetics","Rifampicin","fund_not_ack","original"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-JLqZ7RwZ3VC2d6ErLGHAtOeMRS_7GCz","dataSources":["Krmt6gt9ktB2s6ARh","wrEvssexmuYudwQw9","9bX4N36CTXtCXNFMd"],"keywords":["abacavir","children","efavirenz","lopinavir","malnutrition","population pharmacokinetics","rifampicin","fund_not_ack","original"],"search_terms":["abacavir","pharmacokinetics","african","children","living","hiv","pooled","analysis","describing","effects","age","malnutrition","common","concomitant","medications","tikiso","mcilleron","burger","gibb","rabie","lee","lallemant","cotton","archary","hennig","denti"],"title":"Abacavir pharmacokinetics in African children living with HIV: a pooled analysis describing the effects of age, malnutrition and common concomitant medications","year":2021}