{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:56:31Z","timestamp":1772780191375,"version":"3.50.1"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The pharmacokinetics of abacavir (ABC) in African children living with HIV (CLHIV) weighing &amp;lt;14 kg and receiving pediatric fixed dose combinations (FDC) according to WHO weight bands dosing are limited. An ABC population pharmacokinetic model was developed to evaluate ABC exposure across different World Health Organization (WHO) weight bands.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Children enrolled in the LIVING study in Kenya and Uganda receiving ABC\/lamivudine (3TC) dispersible tablets (60\/30 mg) according to WHO weight bands. A population approach was used to determine the pharmacokinetic parameters. Monte Carlo simulations were conducted using an in silico population with demographic characteristics associated with African CLHIV. ABC exposures (AUC0\u201324) of 6.4\u201350.4 mg h\/L were used as targets.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Plasma samples were obtained from 387 children. A 1-compartment model with allometric scaling of clearance (CL\/F) and volume of distribution (V\/F) according to body weight best characterized the pharmacokinetic data of ABC. The maturation of ABC CL\/F was characterized using a sigmoidal Emax model dependent on postnatal age (50% of adult CL\/F reached by 0.48 years of age). Exposures to ABC were within the target range for children weighing 6.0\u201324.9 kg, but children weighing 3\u20135.9 kg were predicted to be overexposed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Lowering the ABC dosage to 30 mg twice daily or 60 mg once daily for children weighing 3\u20135.9 kg increased the proportion of children within the target and provided comparable exposures. Further clinical study is required to investigate clinical implications and safety of the proposed alternative ABC doses.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpids\/piad082","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T20:20:44Z","timestamp":1696450844000},"page":"574-580","source":"Crossref","is-referenced-by-count":1,"title":["Abacavir Drug Exposures in African Children Under 14 kg Using Pediatric Solid Fixed Dose Combinations According to World Health Organization Weight Bands"],"prefix":"10.1093","volume":"12","author":[{"given":"Suthunya","family":"Chupradit","sequence":"first","affiliation":[{"name":"PhD\u2019s Degree Program in Pharmacy, Faculty of Pharmacy, Chiang Mai University , Chiang Mai , Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalton C","family":"Wamalwa","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, University of Nairobi , Nairobi , Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Maleche-Obimbo","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, University of Nairobi , Nairobi , Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adeodata R","family":"Kekitiinwa","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine Children\u2019s Foundation , Kampala , Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliet","family":"Mwanga-Amumpaire","sequence":"additional","affiliation":[{"name":"Epicentre , Mbarara , Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A","family":"Bukusi","sequence":"additional","affiliation":[{"name":"Centre for Microbiology Research, Kenya Medical Research Institute , Kisumu , Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Winstone M","family":"Nyandiko","sequence":"additional","affiliation":[{"name":"Department of Child Health and Paediatrics\u2014Moi University, AMPATH and Moi Teaching and Referral Hospital , Eldoret , Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph K","family":"Mbuthia","sequence":"additional","affiliation":[{"name":"Gertrude\u2019s Children\u2019s Hospital , Nairobi , Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alistair","family":"Swanson","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases Initiative , Geneva , Switzerland"},{"name":"Drugs for Neglected Diseases Initiative , Nairobi , Kenya"},{"name":"Drugs for Neglected Diseases Initiative , New York , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"DNDi Clinical Team","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim R","family":"Cressey","sequence":"additional","affiliation":[{"name":"AMS\/IRD Research Collaboration, Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai , Thailand"},{"name":"Department of Molecular & Clinical Pharmacology, University of Liverpool , Liverpool , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baralee","family":"Punyawudho","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University , Chiang Mai , Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Musiime","sequence":"additional","affiliation":[{"name":"Joint Clinical Research Centre , Kampala , Uganda"},{"name":"Department of Paediatrics and Child Health, Makerere University , Kampala , 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