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Intrathecal delivery of a recombinant human ASA (TAK\u2010611, formerly SHP611) is under development as a potential therapy for MLD. We used serum and cerebrospinal fluid (CSF) TAK\u2010611 concentrations measured during the phase I\/II trial of intrathecal TAK\u2010611 to develop a pharmacokinetic (PK) model describing drug disposition. CSF data were well characterized by a two\u2010compartment model in the central nervous system (CNS); a single central compartment described the serum data. Estimated parameters suggested rapid distribution of TAK\u2010611 from CSF into the putative brain tissue compartment, with persistence in the brain between doses (median distributive and terminal half\u2010lives in the CNS: 1.02 and 477\u00a0hours, respectively). This model provides a valuable basis for understanding the PK distribution of TAK\u2010611 and for PK\/pharmacodynamic analyses of functional outcomes.<\/jats:p>","DOI":"10.1002\/cpt.1752","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T11:39:07Z","timestamp":1577101147000},"page":"1394-1404","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Pharmacokinetic Modeling of Intrathecally Administered Recombinant Human Arylsulfatase A (TAK\u2010611) in Children With Metachromatic Leukodystrophy"],"prefix":"10.1111","volume":"107","author":[{"given":"Steven","family":"Troy","sequence":"first","affiliation":[{"name":"Shire (a member of the Takeda group of companies) Lexington Massachusetts USA"},{"name":"Radius Health Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Wasilewski","sequence":"additional","affiliation":[{"name":"Shire (a member of the Takeda group of companies) Lexington Massachusetts USA"},{"name":"ID Remedies LLC Medford Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Beusmans","sequence":"additional","affiliation":[{"name":"Metrum Research Group Tariffville Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.J.","family":"Godfrey","sequence":"additional","affiliation":[{"name":"Metrum Research Group Tariffville Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,25]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2008.00648.x"},{"key":"e_1_2_11_2_1","volume-title":"Scriver's Online Metabolic and Molecular Bases of Inherited Disease","author":"Figura K.","year":"2001"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2014.10.001"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-9-18"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1253412"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2011.04028.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2008.275"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2013.01.010"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-015-0313-y"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-015-0116-7"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-017-0635-z"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623311409595"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030341"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.36"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0195186"},{"key":"e_1_2_11_16_1","first-page":"S396","article-title":"Safety and efficacy of intrathecal delivery of recombinant human arylsulfatase A in children with late\u2010infantile metachromatic leukodystrophy","volume":"84","author":"Giugliani R.","year":"2018","journal-title":"Ann. 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