{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:18:28Z","timestamp":1790882308466,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Children with primary immunodeficiency (PID) and secondary antibody deficiency (SAD) often require immunoglobulin replacement therapy due to low plasma immunoglobulin G (IgG) levels and recurrent infections. Existing pharmacokinetic models for immunoglobulin in PID patients predominantly focus on adults, with limited attention to secondary antibody deficiencies and a lesser emphasis on paediatric populations. This study aims to investigate the pharmacokinetic properties of IgG in paediatric patients with PID and SAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Population pharmacokinetic analysis for PID and SAD children treated with intravenous immunoglobulin at a tertiary paediatric centre was conducted using NONMEM\u00ae (7.5.1). Dosing simulations to achieve therapeutic levels of 6 and 8 gL\n                      <jats:sup>\u22121<\/jats:sup>\n                      were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A population pharmacokinetic analysis of 64 patients (median age 4.08 years, range 0.06\u201316.8) was performed. A two\u2010compartment model with first\u2010order elimination, incorporating both additive and proportional residual error, adequately described the data. Interindividual variability was modelled on clearance, volume of distribution and baseline IgG levels, with allometric scaling to a 70\u2010kg body weight applied a priori. The estimated clearance was 0.308 L\n                      <jats:sup>\u22121<\/jats:sup>\n                      day\n                      <jats:sup>\u22121<\/jats:sup>\n                      70 kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      (95% CI 0.23, 0.67), and the volume of distribution was 10.96 L\n                      <jats:sup>\u22121<\/jats:sup>\n                      70 kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      (95% CI 5.97, 15.79). Patients with SAD exhibited a lower clearance rate of 54% compared with PID patients. Dosing simulations indicated that the recommended SAD dosing regimen maintained therapeutic IgG levels in the simulated population. However, only 44.8% to 51.9% of patients with PID achieved target IgG levels with the standard regimen.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides insights into immunoglobulin pharmacokinetics in paediatric PID and SAD patients, guiding optimised dosing strategies. Administering a loading dose would improve the probability of maintaining therapeutic IgG levels during the 4\u2010week dosing interval.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70420","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T03:35:46Z","timestamp":1766979346000},"page":"1641-1651","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetic modelling of intravenous immunoglobulin in children with primary immunodeficiencies and secondary antibody deficiencies"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1010-8085","authenticated-orcid":false,"given":"Iek Leng","family":"Cheng","sequence":"first","affiliation":[{"name":"Infection, Immunity and Inflammation Research &amp; Teaching Department, UCL GOS Institute of Child Health University of London  London UK"},{"name":"Pharmacy Department Great Ormond Street Hospital  London Greater London 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