{"doi":"10.1093/jac/dkae259","title":"Lamivudine dosing for preterm infants exposed to HIV: a population pharmacokinetic modelling and simulation study","abstract":"OBJECTIVES: To develop a pragmatic twice daily lamivudine dosing strategy for preterm infants from 24 to 37 completed weeks of gestation. METHODS: Data were combined from eight pharmacokinetic studies in neonates and infants receiving lamivudine oral solution. A population pharmacokinetic model was developed using non-linear mixed effects regression. Different lamivudine dosing strategies, stratified by gestational age at birth (GA) bands, were simulated in a virtual population of preterm infants, aimed at maintaining lamivudine drug exposures (AUC0-12) within a reference target range of 2.95 to 13.25 µg·h/mL, prior to switching to WHO-weight band doses when ≥4 weeks of age and weighing ≥3 kg. RESULTS: A total of 154 infants (59% female) contributed 858 lamivudine plasma concentrations. Median (range) GA at birth was 38 (27-41) weeks. At the time of first pharmacokinetic sampling infants were older with median postnatal age (PNA) of 6.3 (0.52-26.6) weeks. Lamivudine concentrations were described by a one-compartment model, with CL/F and V/F allometrically scaled to weight. Maturation of CL/F was described using an Emax model based on PNA. CL/F was also adjusted on GA to allow extrapolation for extreme prematurity. Simulations predicted an optimal lamivudine dosing for infants GA ≥24 to <30 weeks of 2 mg/kg twice daily from birth until weighing 3 kg; and for GA ≥30 to <37 weeks, 2 mg/kg twice daily for the first 4 weeks of life, followed by 4 mg/kg twice daily until weighing 3 kg. CONCLUSIONS: Model-based predictions support twice daily pragmatic GA band dosing of lamivudine for preterm infants, but clinical validation is warranted.","journal":"Journal of Antimicrobial Chemotherapy","year":2024,"id":480921,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":330622,"name":"Edmund V. Capparelli","orcid":"0000-0002-1630-0505","position":1,"is_corresponding":false},{"id":354235,"name":"Mark Mirochnick","orcid":"0000-0002-3600-1502","position":2,"is_corresponding":false},{"id":534127,"name":"Diana F. Clarke","orcid":null,"position":3,"is_corresponding":false},{"id":295667,"name":"Mark F. Cotton","orcid":"0000-0003-2559-6034","position":4,"is_corresponding":false},{"id":431953,"name":"Roger Shapiro","orcid":"0000-0002-4832-6275","position":5,"is_corresponding":false},{"id":377555,"name":"Katie McCarthy","orcid":null,"position":6,"is_corresponding":false},{"id":346911,"name":"Jack Moye","orcid":"0000-0001-9976-8586","position":7,"is_corresponding":false},{"id":447851,"name":"Avy Violari","orcid":"0000-0002-9437-776X","position":8,"is_corresponding":false},{"id":398172,"name":"Kulkanya Chokephaibulkit","orcid":"0000-0002-0140-4600","position":9,"is_corresponding":false},{"id":24184,"name":"Elaine J. Abrams","orcid":"0000-0001-7938-8981","position":10,"is_corresponding":false},{"id":295672,"name":"Martina Penazzato","orcid":"0000-0001-5485-8692","position":11,"is_corresponding":false},{"id":255289,"name":"Theodore Ruel","orcid":"0000-0002-1105-9126","position":12,"is_corresponding":false},{"id":354236,"name":"Tim R. Cressey","orcid":"0000-0002-8106-0974","position":13,"is_corresponding":false},{"id":354231,"name":"Adrie Bekker","orcid":"0000-0003-3836-3432","position":0,"is_corresponding":true}],"reference_count":12,"raw_metadata":null,"created_at":"2026-07-19T02:07:02.142014Z","pmid":"39092932","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}