{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:35:31Z","timestamp":1790127331088,"version":"4.0.1"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>N\u2010acetylcysteine (NAC) has been used in patients with cerebral adrenoleukodystrophy as an antioxidant agent in association with hematopoietic stem cell transplant (HSCT). However, an understanding of the pharmacokinetic characteristics of intravenous NAC dosing in these patients is limited. If and how NAC pharmacokinetics change following the transplant is unknown. Toward that end, a total of 260 blood samples obtained from 18 pediatric patients with inherited metabolic disorders who underwent HSCT were included in a population pharmacokinetic analysis using nonlinear mixed\u2010effects modeling. NAC clearance (CL) and volume of distribution (V) were explored on 3 occasions: \u20137, +7, and +21 days relative to transplant. Additionally, the effect of transplant procedure on NAC disposition was explored by accounting for between\u2010occasion variability. The covariate OCC was modeled as a fixed\u2010effect parameter on CL and\/or V1. A 2\u2010compartment model adequately described the pharmacokinetics of total NAC. Weight\u2010based allometric scaling on pharmacokinetic parameters was assumed using standard coefficients. Estimates for CL, central (V1), and peripheral volume (V2), and intercompartment clearance were 14.7 L\/h, 23.2 L, 17.1 L, 3.99 L\/h, respectively, for a 70\u2010kg person. The data only supported between\u2010subject variability in CL (12%) and V1 (41%). Residual variability was estimated to be 16%. HSCT did not change CL and V1 significantly, and analysis across occasions did not reveal any trends. Pharmacokinetic parameter estimates were in general comparable to those reported previously in different populations. These results suggest that dosing of NAC does not need to be altered following HSCT.<\/jats:p>","DOI":"10.1002\/jcph.1943","type":"journal-article","created":{"date-parts":[[2021,7,18]],"date-time":"2021-07-18T11:46:20Z","timestamp":1626608780000},"page":"1638-1645","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Population Pharmacokinetic Analysis of N\u2010Acetylcysteine in Pediatric Patients With Inherited Metabolic Disorders Undergoing Hematopoietic Stem Cell Transplant"],"prefix":"10.1002","volume":"61","author":[{"given":"Siddhee A.","family":"Sahasrabudhe","sequence":"first","affiliation":[{"name":"Center for Orphan Drug Research Department of Experimental and Clinical Pharmacology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena V.","family":"Kartha","sequence":"additional","affiliation":[{"name":"Center for Orphan Drug Research Department of Experimental and Clinical Pharmacology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Perth Children's Hospital  Nedlands WA Australia"},{"name":"Division of Pediatric Blood and Marrow Transplantation University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Basso","sequence":"additional","affiliation":[{"name":"Division of Pediatric Blood and Marrow Transplantation University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usha","family":"Mishra","sequence":"additional","affiliation":[{"name":"Center for Orphan Drug Research Department of Experimental and Clinical Pharmacology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Cloyd","sequence":"additional","affiliation":[{"name":"Center for Orphan Drug Research Department of Experimental and Clinical Pharmacology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Orchard","sequence":"additional","affiliation":[{"name":"Division of Pediatric Blood and Marrow Transplantation University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Brundage","sequence":"additional","affiliation":[{"name":"Center for Orphan Drug Research Department of Experimental and Clinical Pharmacology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa D.","family":"Coles","sequence":"additional","affiliation":[{"name":"Center for Orphan Drug Research Department of 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