{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:55:16Z","timestamp":1781535316781,"version":"3.54.5"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Pharmacokinet"],"published-print":{"date-parts":[[2022,2]]},"DOI":"10.1007\/s40262-021-01068-0","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T03:20:22Z","timestamp":1633576822000},"page":"321-333","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Pharmacokinetic\/Pharmacodynamic Modelling of Allopurinol, its Active Metabolite Oxypurinol, and Biomarkers Hypoxanthine, Xanthine and Uric Acid in Hypoxic-Ischemic Encephalopathy Neonates"],"prefix":"10.1007","volume":"61","author":[{"given":"Wan-Yu","family":"Chu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim V.","family":"Annink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Laura","family":"Nijstad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian A.","family":"Maiwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schroth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loubna el","family":"Bakkali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"van Bel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon J. N. L.","family":"Benders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam M.","family":"van Weissenbruch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Hagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel R.","family":"Franz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P. C.","family":"Dorlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-5105","authenticated-orcid":false,"given":"Karel","family":"Allegaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alwin D. R.","family":"Huitema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the ALBINO Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel R.","family":"Franz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"R\u00fcdiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian F.","family":"Poets","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"van Bel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Allegaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Naulaers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Bassler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Klebermass-Schrehof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximo","family":"Vento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hercilia","family":"Guimaraes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Stiris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Mauro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo","family":"Mets\u00e4ranta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sampsa","family":"Vanhatalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Mazela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannique","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"1068_CR1","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/pr.2013.206","volume":"74","author":"ACC Lee","year":"2013","unstructured":"Lee ACC, Kozuki N, Blencowe H, Vos T, Bahalim A, Darmstadt GL, et al. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr Res. 2013;74:50\u201372.","journal-title":"Pediatr Res"},{"key":"1068_CR2","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1056\/NEJMoa0900854","volume":"361","author":"DV Azzopardi","year":"2009","unstructured":"Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009;361:1349\u201358.","journal-title":"N Engl J Med"},{"key":"1068_CR3","first-page":"CD003311","volume":"1","author":"SE Jacobs","year":"2013","unstructured":"Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013;1:CD003311.","journal-title":"Cochrane Database Syst Rev"},{"key":"1068_CR4","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1056\/NEJMoa1315788","volume":"371","author":"D Azzopardi","year":"2014","unstructured":"Azzopardi D, Strohm B, Marlow N, Brocklehurst P, Deierl A, Eddama O, et al. Effects of hypothermia for perinatal asphyxia on childhood outcomes. N Engl J Med. 2014;371:140\u20139.","journal-title":"N Engl J Med"},{"key":"1068_CR5","doi-asserted-by":"publisher","first-page":"351","DOI":"10.4324\/9781315150451-17","volume":"351","author":"D Webster","year":"2019","unstructured":"Webster D. Neonatal brain injury. Neonatal Intensive Care Nurs. 2019;351:351\u201374.","journal-title":"Neonatal Intensive Care Nurs."},{"key":"1068_CR6","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1053\/j.nainr.2011.07.004","volume":"11","author":"KA Allen","year":"2011","unstructured":"Allen KA, Brandon DH. Hypoxic ischemic encephalopathy: pathophysiology and experimental treatments. Newborn Infant Nurs Rev. 2011;11:125\u201333.","journal-title":"Newborn Infant Nurs Rev"},{"key":"1068_CR7","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1056\/NEJM198501173120305","volume":"312","author":"FH Epstein","year":"1985","unstructured":"Epstein FH, McCord JM. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med. 1985;312:159\u201363.","journal-title":"N Engl J Med"},{"key":"1068_CR8","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1053\/j.semperi.2015.12.003","volume":"40","author":"FV van Bel","year":"2016","unstructured":"van Bel FV, Groenendaal F. Drugs for neuroprotection after birth asphyxia: pharmacologic adjuncts to hypothermia. Semin Perinatol. 2016;40:152\u20139.","journal-title":"Semin Perinatol"},{"key":"1068_CR9","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1203\/00006450-199004000-00003","volume":"27","author":"C Palmer","year":"1990","unstructured":"Palmer C, Vannucci RC, Towfighi J. Reduction of perinatal hypoxic-ischemic brain damage with allopurinol. Pediatr Res. 1990;27:332\u20136.","journal-title":"Pediatr Res"},{"key":"1068_CR10","doi-asserted-by":"publisher","first-page":"3221","DOI":"10.1242\/jeb.01022","volume":"207","author":"DS Warner","year":"2004","unstructured":"Warner DS, Sheng H, Batini\u0107-Haberle I. Oxidants, antioxidants and the ischemic brain. J Exp Biol. 2004;207:3221\u201331.","journal-title":"J Exp Biol"},{"key":"1068_CR11","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/0014-5793(87)81458-8","volume":"213","author":"PC Moorhouse","year":"1987","unstructured":"Moorhouse PC, Grootveld M, Halliwell B, Quinlan JG, Gutteridge JMC. Allopurinol and oxypurinol are hydroxyl radical scavengers. FEBS Lett. 1987;213:23\u20138.","journal-title":"FEBS Lett"},{"key":"1068_CR12","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/S0304-3940(98)00303-6","volume":"248","author":"M Shadid","year":"1998","unstructured":"Shadid M, Buonocore G, Groenendaal F, Moison R, Ferrali M, Berger HM, et al. Effect of deferoxamine and allopurinol on non-protein-bound iron concentrations in plasma and cortical brain tissue of newborn lambs following hypoxia-ischemia. Neurosci Lett. 1998;248:5\u20138.","journal-title":"Neurosci Lett"},{"key":"1068_CR13","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1515\/jpm.2011.025","volume":"39","author":"D Boda","year":"2011","unstructured":"Boda D. Results of and further prevention of hypoxic fetal brain damage by inhibition of xanthine oxidase enzyme with allopurinol. J Perinat Med. 2011;39:441\u20134.","journal-title":"J Perinat Med"},{"key":"1068_CR14","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.brainres.2005.11.061","volume":"1073\u20131074","author":"PJ Marro","year":"2006","unstructured":"Marro PJ, Mishra OP, Delivoria-Papadopoulos M. Effect of allopurinol on brain adenosine levels during hypoxia in newborn piglets. Brain Res. 2006;1073\u20131074:444\u201350.","journal-title":"Brain Res"},{"key":"1068_CR15","doi-asserted-by":"publisher","first-page":"5935","DOI":"10.2174\/1381612823666170918123307","volume":"23","author":"KV Annink","year":"2018","unstructured":"Annink KV, Franz AR, Derks JB, R\u00fcdiger M, van Bel F, Benders MJNL. Allopurinol: old drug, new indication in neonates? Curr Pharm Des. 2018;23:5935\u201342.","journal-title":"Curr Pharm Des"},{"key":"1068_CR16","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/s12887-019-1566-8","volume":"19","author":"CA Maiwald","year":"2019","unstructured":"Maiwald CA, Annink KV, R\u00fcdiger M, Benders MJNL, Van Bel F, Allegaert K, et al. Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III). BMC Pediatr. 2019;19:210.","journal-title":"BMC Pediatr"},{"key":"1068_CR17","doi-asserted-by":"publisher","first-page":"623","DOI":"10.2165\/00003088-200746080-00001","volume":"46","author":"RO Day","year":"2007","unstructured":"Day RO, Graham GG, Hicks M, McLachlan AJ, Stocker SL, Williams KM. Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Clin Pharmacokinet. 2007;46:623\u201344.","journal-title":"Clin Pharmacokinet"},{"key":"1068_CR18","doi-asserted-by":"publisher","first-page":"343","DOI":"10.2165\/00003088-198611050-00001","volume":"11","author":"GAC Murrell","year":"1986","unstructured":"Murrell GAC, Rapeport WG. Clinical pharmacokinetics of allopurinol. Clin Pharmacokinet. 1986;11:343\u201353.","journal-title":"Clin Pharmacokinet"},{"key":"1068_CR19","doi-asserted-by":"publisher","first-page":"109672","DOI":"10.1039\/C6RA19197E","volume":"6","author":"S Mirzaei","year":"2016","unstructured":"Mirzaei S, Taherpour AA, Mohamadi S. Mechanistic study of allopurinol oxidation using aldehyde oxidase, xanthine oxidase and cytochrome P450 enzymes. RSC Adv. 2016;6:109672\u201380.","journal-title":"RSC Adv"},{"key":"1068_CR20","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1007\/s00228-013-1478-8","volume":"69","author":"DFB Wright","year":"2013","unstructured":"Wright DFB, Stamp LK, Merriman TR, Barclay ML, Duffull SB, Holford NHG. The population pharmacokinetics of allopurinol and oxypurinol in patients with gout. Eur J Clin Pharmacol. 2013;69:1411\u201321.","journal-title":"Eur J Clin Pharmacol"},{"key":"1068_CR21","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1046\/j.1365-2125.1999.00041.x","volume":"48","author":"K Turnheim","year":"1999","unstructured":"Turnheim K, Krivanek P, Oberbauer R. Pharmacokinetics and pharmacodynamics of allopurinol in elderly and young subjects. Br J Clin Pharmacol. 1999;48:501\u20139.","journal-title":"Br J Clin Pharmacol"},{"key":"1068_CR22","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1111\/j.1365-2125.2012.04207.x","volume":"74","author":"SL Stocker","year":"2012","unstructured":"Stocker SL, Mclachlan AJ, Savic RM, Kirkpatrick CM, Graham GG, Williams KM, et al. The pharmacokinetics of oxypurinol in people with gout. Br J Clin Pharmacol. 2012;74:477\u201389.","journal-title":"Br J Clin Pharmacol"},{"key":"1068_CR23","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/0006-2952(88)90739-3","volume":"37","author":"T Spector","year":"1988","unstructured":"Spector T. Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical. Biochem Pharmacol. 1988;37:349\u201352.","journal-title":"Biochem Pharmacol"},{"key":"1068_CR24","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1038\/jid.2014.371","volume":"135","author":"H Sierra","year":"2015","unstructured":"Sierra H, Cordova M, Chen CSJ, Rajadhyaksha M. Confocal imaging-guided laser ablation of basal cell carcinomas: an ex vivo study. J Invest Dermatol. 2015;135:612\u20135.","journal-title":"J Invest Dermatol"},{"key":"1068_CR25","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1542\/peds.94.6.820","volume":"94","author":"SP McGaurn","year":"1994","unstructured":"McGaurn SP, Davis LE, Krawczeniuk MM, Murphy JD, Jacobs ML, Norwood WI, et al. The pharmacokinetics of injectable allopurinol in newborns with the hypoplastic left heart syndrome. Pediatrics. 1994;94:820\u20133.","journal-title":"Pediatrics"},{"key":"1068_CR26","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1097\/01.ftd.0000211808.74192.86","volume":"28","author":"C van Kesteren","year":"2006","unstructured":"van Kesteren C, Benders MJNL, Groenendaal F, Van Bel F, Ververs FFT, Rademaker CMA. Population pharmacokinetics of allopurinol in full-term neonates with perinatal asphyxia. Ther Drug Monit. 2006;28:339\u201344.","journal-title":"Ther Drug Monit"},{"key":"1068_CR27","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1002\/cpt.1917","volume":"108","author":"LMA Favi\u00e9","year":"2020","unstructured":"Favi\u00e9 LMA, de Haan TR, Bijleveld YA, Rademaker CMA, Egberts TCG, Nuytemans DHGM, et al. Prediction of drug exposure in critically ill encephalopathic neonates treated with therapeutic hypothermia based on a pooled population pharmacokinetic analysis of seven drugs and five metabolites. Clin Pharmacol Ther. 2020;108:1098\u2013106.","journal-title":"Clin Pharmacol Ther"},{"key":"1068_CR28","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1542\/peds.101.2.185","volume":"101","author":"F Van Bel","year":"1998","unstructured":"Van Bel F, Shadid M, Moison RMW, Dorrepaal CA, Fontijn J, Monteiro L, et al. Effect of allopurinol on postasphyxial free radical formation, cerebral hemodynamics, and electrical brain activity. Pediatrics. 1998;101:185\u201393.","journal-title":"Pediatrics"},{"key":"1068_CR29","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1136\/adc.2005.086652","volume":"91","author":"MJNL Benders","year":"2006","unstructured":"Benders MJNL, Bos AF, Rademaker CMA, Rijken M, Torrance HL, Groenendaal F, et al. Early postnatal allopurinol does not improve short term outcome after severe birth asphyxia. Arch Dis Child Fetal Neonatal Ed. 2006;91:163\u20135.","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"1068_CR30","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/S0006-8993(02)03843-X","volume":"963","author":"C Peeters","year":"2003","unstructured":"Peeters C, Hoelen D, Groenendaal F, Van Bel F, B\u00e4r D. Deferoxamine, allopurinol and oxypurinol are not neuroprotective after oxygen\/glucose deprivation in an organotypic hippocampal model, lacking functional endothelial cells. Brain Res. 2003;963:72\u201380.","journal-title":"Brain Res"},{"key":"1068_CR31","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1227\/00006123-198707000-00008","volume":"21","author":"P Kim","year":"1987","unstructured":"Kim P, Yaksh TL, Romero SD, Sundt TM. Production of uric acid in cerebrospinal fluid after subarachnoid hemorrhage in dogs: Investigation of the possible role of xanthine oxidase in chronic vasospasm. Neurosurgery. 1987;21:39\u201344.","journal-title":"Neurosurgery"},{"key":"1068_CR32","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.cmpb.2010.04.018","volume":"101","author":"RJ Keizer","year":"2011","unstructured":"Keizer RJ, van Benten M, Beijnen JH, Schellens JHM, Huitema ADR. Pira\u00f1a and PCluster: a modeling environment and cluster infrastructure for NONMEM. Comput Methods Programs Biomed. 2011;101:72\u20139.","journal-title":"Comput Methods Programs Biomed"},{"key":"1068_CR33","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1126\/science.276.5309.122","volume":"276","author":"GB West","year":"1997","unstructured":"West GB, Brown JH, Enquist BJ. A general model for the origin of allometric scaling laws in biology. Science. 1997;276:122\u20136.","journal-title":"Science"},{"key":"1068_CR34","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s00467-008-0997-5","volume":"24","author":"MM Rhodin","year":"2009","unstructured":"Rhodin MM, Anderson BJ, Peters AM, Coulthard MG, Wilkins B, Cole M, et al. Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr Nephrol. 2009;24:67\u201376.","journal-title":"Pediatr Nephrol"},{"key":"1068_CR35","doi-asserted-by":"publisher","first-page":"211","DOI":"10.3389\/fped.2019.00211","volume":"7","author":"TS Rosenkrantz","year":"2019","unstructured":"Rosenkrantz TS, Hussain Z, Fitch RH. Sex differences in brain injury and repair in newborn infants: clinical evidence and biological mechanisms. Front Pediatr. 2019;7:211.","journal-title":"Front Pediatr"},{"key":"1068_CR36","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.cmpb.2007.12.002","volume":"90","author":"E Comets","year":"2008","unstructured":"Comets E, Brendel K, Mentr\u00e9 F. Computing normalised prediction distribution errors to evaluate nonlinear mixed-effect models: the npde add-on package for R. Comput Methods Programs Biomed. 2008;90:154\u201366.","journal-title":"Comput Methods Programs Biomed"},{"key":"1068_CR37","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1208\/s12248-016-9866-5","volume":"18","author":"Y Aoki","year":"2016","unstructured":"Aoki Y, Nordgren R, Hooker AC. Preconditioning of nonlinear mixed effects models for stabilisation of variance-covariance matrix computations. AAPS J. 2016;18:505.","journal-title":"AAPS J"},{"key":"1068_CR38","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s10928-016-9468-y","volume":"43","author":"S Ueckert","year":"2016","unstructured":"Ueckert S, Karlsson MO, Hooker AC. Accelerating Monte Carlo power studies through parametric power estimation. J Pharmacokinet Pharmacodyn J Pharmacokinet Pharmacodyn. 2016;43:223\u201334.","journal-title":"J Pharmacokinet Pharmacodyn. J Pharmacokinet Pharmacodyn"},{"key":"1068_CR39","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1007\/s10928-017-9542-0","volume":"44","author":"AG Dosne","year":"2017","unstructured":"Dosne AG, Bergstrand M, Karlsson MO. An automated sampling importance resampling procedure for estimating parameter uncertainty. J Pharmacokinet Pharmacodyn. 2017;44:509\u201320.","journal-title":"J Pharmacokinet Pharmacodyn"},{"key":"1068_CR40","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1002\/pst.400","volume":"9","author":"S Yang","year":"2010","unstructured":"Yang S, Roger J. Evaluations of Bayesian and maximum likelihood methods in PK models with below-quantification-limit data. Pharm Stat. 2010;9:313\u201330.","journal-title":"Pharm Stat"},{"key":"1068_CR41","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1002\/cpt1978235598","volume":"23","author":"K Hande","year":"1978","unstructured":"Hande K, Reed E, Chabner B. Allopurinol kinetics. Clin Pharmacol Ther. 1978;23:598\u2013605.","journal-title":"Clin Pharmacol Ther"},{"key":"1068_CR42","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/978-1-4684-4553-4_31","volume":"165 Pt A","author":"DJ Nelson","year":"1984","unstructured":"Nelson DJ, Elion GB. Metabolic studies of high doses of allopurinol in humans. Adv Exp Med Biol. 1984;165 Pt A:167\u201370.","journal-title":"Adv Exp Med Biol"},{"key":"1068_CR43","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1080\/00498254.2019.1626029","volume":"50","author":"C Beedham","year":"2020","unstructured":"Beedham C. Aldehyde oxidase; new approaches to old problems. Xenobiotica. 2020;50:34\u201350.","journal-title":"Xenobiotica"},{"key":"1068_CR44","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1203\/00006450-199704000-00010","volume":"41","author":"PJ Marro","year":"1997","unstructured":"Marro PJ, Baumgart S, Delivoria-Papadopoulos M, Zirin S, Corcoran L, McGaurn SP, et al. Purine metabolism and inhibition of xanthine oxidase in severely hypoxic neonates going onto extracorporeal membrane oxygenation. Pediatr Res. 1997;41:513\u201323.","journal-title":"Pediatr Res"},{"key":"1068_CR45","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/0002-9343(68)90008-9","volume":"45","author":"GB Elion","year":"1968","unstructured":"Elion GB, Y\u00fc TF, Gutman AB, Hitchings GH. Renal clearance of oxipurinol, the chief metabolite of allopurinol. Am J Med. 1968;45:69\u201377.","journal-title":"Am J Med"},{"key":"1068_CR46","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/nature742","volume":"417","author":"A Enomoto","year":"2002","unstructured":"Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH, et al. Molecular identification of a renal urate-anion exchanger that regulates blood urate levels. Nature. 2002;417:447\u201352.","journal-title":"Nature"},{"key":"1068_CR47","first-page":"1791","volume":"33","author":"T Iwanaga","year":"2005","unstructured":"Iwanaga T, Kobayashi D, Hirayama M, Maeda T, Tamai I. Involvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone. Drug Metab Dispos. 2005;33:1791\u20135.","journal-title":"Drug Metab Dispos"},{"key":"1068_CR48","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/BF00606429","volume":"22","author":"H Breithaupt","year":"1982","unstructured":"Breithaupt H, Tittel M. Kinetics of allopurinol after single intravenous and oral doses\u2014noninteraction with benzbromarone and hydrochlorothiazide. Eur J Clin Pharmacol. 1982;22:77\u201384.","journal-title":"Eur J Clin Pharmacol"},{"key":"1068_CR49","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1002\/cpt.1516","volume":"106","author":"KWK Cheung","year":"2019","unstructured":"Cheung KWK, van Groen BD, Spaans E, van Borselen MD, de Bruijn ACJM, Simons-Oosterhuis Y, et al. A comprehensive analysis of ontogeny of renal drug transporters: mRNA analyses, quantitative proteomics, and localization. Clin Pharmacol Ther. 2019;106:1083\u201392.","journal-title":"Clin Pharmacol Ther"},{"issue":"6","key":"1068_CR50","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1053\/j.ackd.2012.07.010","volume":"19","author":"B Stiburkova","year":"2012","unstructured":"Stiburkova B, Bleyer AJ. Changes in serum urate and urate excretion with age. Adv Chronic Kidney Dis. 2012;19(6):372\u20136.","journal-title":"Adv Chronic Kidney Dis"}],"container-title":["Clinical Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-021-01068-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40262-021-01068-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-021-01068-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T14:18:45Z","timestamp":1706192325000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40262-021-01068-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,7]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["1068"],"URL":"https:\/\/doi.org\/10.1007\/s40262-021-01068-0","relation":{},"ISSN":["0312-5963","1179-1926"],"issn-type":[{"value":"0312-5963","type":"print"},{"value":"1179-1926","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,7]]},"assertion":[{"value":"10 August 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The ALBINO project is funded under the Horizon 2020 Framework EU Program call H2020-PHC-2015-two-stage, grant 667224. The research on the PK during whole-body hypothermia (KA) is further supported by the iPREDICT project (FWO senior research project, fundamental research, G0D0520N).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Wan-Yu Chu, Kim Annink, Laura Nijstad, Christian Maiwald, Michael Schroth, Loubna el Bakkali, Frank van Bel, Manon Benders, Mirjam van Weissenbruch, Anja Hagen, Axel Franz, Thomas Dorlo, Karel Allegaert, and Alwin Huitema have no conflicts of interest to declare.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest\/Competing interests"}},{"value":"The data used in this study were performed in accordance with the Declaration of Helsinki and the guidelines of Good Clinical Practice (GCP). The ALBINO study was granted by Institutional Review Boards and Independent Ethics Committees. The Medical Ethics Committee of the University Medical Centre Utrecht and the Central Committee on Human Research approved the study, including the specific PK substudy for The Netherlands (NL57237.041.16). The German Federal Authority (EudraCT 2016-000222-19), as well as the leading Ethics Committee T\u00fcbingen, approved the study for Germany.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Short oral consent was obtained from at least one parent before administering the study medication. After the first dose, but before the (potential) second dose, full written parental consent was obtained. In case parents did not sign the informed consent, blood samples already collected shortly after birth were destroyed.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The raw data are available upon reasonable request by an e-mail to the corresponding author, while blinding for group allocation should be respected until the primary outcome analysis has been finalized.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and material"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"Protocol development and study conduct: KVA, MS, CM, LEB, FVB, MB, MVW, AH, AF, KA. Ethics and study registration: KVA, FVB, MB, AF. Study recruitment and data collection: KVA, MS, CM, LEB, FVB, MB, MVW, AH, AF. Modelling: WYC, LN, TD, ADRH. Drafting of the manuscript: WYC, KVA, LN, TD, KA, ADRH. All authors have read and commented on the manuscript and have approved the submitted version.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author contributions"}}]}}