{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:37:13Z","timestamp":1792525033232,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2008,9,22]],"date-time":"2008-09-22T00:00:00Z","timestamp":1222041600000},"content-version":"vor","delay-in-days":2974,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2000,8]]},"abstract":"<jats:p> <jats:bold>\n            <jats:italic>Aims<\/jats:italic>\n          <\/jats:bold> The aims of this study were to describe paracetamol pharmacokinetics in neonates and infants.<\/jats:p><jats:p> <jats:bold>\n            <jats:italic>Methods<\/jats:italic>\n          <\/jats:bold> Infants in their first 3 months of life (<jats:italic>n<\/jats:italic>\u2003=\u200330) were randomised to sequentially receive one of three paracetamol formulations (dose 30\u201340\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) over a 2 day period. The formulations were (a) elixir, (b) glycogelatin capsule suppository and (c) triglyceride base suppository. Approximately six blood samples were taken after each dose over the subsequent 10\u201316\u2003h. Data were analysed using a nonlinear mixed effect model. These neonatal and infant data were then included with data from four published studies of paracetamol pharmacokinetics (<jats:italic>n<\/jats:italic>\u2003=\u2003221) and age\u2010related pharmacokinetic changes investigated.<\/jats:p><jats:p> <jats:bold>\n            <jats:italic>Results<\/jats:italic>\n          <\/jats:bold> Population pharmacokinetic parameter estimates and their coefficients of variation (CV%) for a one compartment model with first order input, lag time and first order elimination were volume of distribution 69.9 (18%) l and clearance 13.0 (41%) l h<jats:sup>\u22121<\/jats:sup> (standardized to a 70\u2003kg person). The volume of distribution decreased exponentially with a half\u2010life of 1.9\u2003days from 120\u2003l 70\u2003kg<jats:sup>\u22121<\/jats:sup> at birth to 69.9\u2003l 70\u2003kg<jats:sup>\u22121<\/jats:sup> by 14\u2003days. Clearance increased from birth (4.9\u2003l\u2003h<jats:sup>\u22121<\/jats:sup> 70\u2003kg<jats:sup>\u22121<\/jats:sup>) with a half\u2010life of 3.25\u2003months to reach 12.4\u2003l\u2003h<jats:sup>\u22121<\/jats:sup> 70\u2003kg<jats:sup>\u22121<\/jats:sup> by 12\u2003months. The absorption half\u2010life (<jats:italic>t<\/jats:italic><jats:sub>abs<\/jats:sub>) for the oral preparation was 0.13 (154%) h with a lag time (<jats:italic>t<\/jats:italic><jats:sub>lag<\/jats:sub>) of 0.39\u2003h (31%). Absorption parameters for the triglyceride base and capsule suppositories were <jats:italic>t<\/jats:italic><jats:sub>abs<\/jats:sub> 1.34 (90%) h, <jats:italic>t<\/jats:italic><jats:sub>lag<\/jats:sub> 0.14\u2003h (31%) and <jats:italic>t<\/jats:italic><jats:sub>abs<\/jats:sub> 0.65 (63%) h, <jats:italic>t<\/jats:italic><jats:sub>lag<\/jats:sub> 0.54\u2003h (31%), respectively. The <jats:italic>t<\/jats:italic><jats:sub>abs<\/jats:sub> for elixir and capsule suppository in children under 3\u2003months were 3.68 and 1.51 times greater than children over 3\u2003months. The relative bioavailability of rectal formulations compared with elixir were 0.67 (30%) and 0.61 (23%) for the triglyceride base and capsule suppositories, respectively.<\/jats:p><jats:p> <jats:bold>\n            <jats:italic>Conclusions<\/jats:italic>\n          <\/jats:bold> Total body clearance of paracetamol at birth is 62% and volume of distribution 174% that of older children. A target concentration above 10\u2003mg\u2003l<jats:sup>\u22121<\/jats:sup> in approximately 50% subjects can be achieved by a dose from 45\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> day<jats:sup>\u22121<\/jats:sup> at birth and up to 90\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> day<jats:sup>\u22121<\/jats:sup> in 5\u2010year\u2010old children. A reduced dose of 75\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> day<jats:sup>\u22121<\/jats:sup> in an 8\u2010year\u2010old child is sufficient because clearance is a nonlinear function of weight.<\/jats:p>","DOI":"10.1046\/j.1365-2125.2000.00231.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T04:38:45Z","timestamp":1047357525000},"page":"125-134","source":"Crossref","is-referenced-by-count":156,"title":["A model for size and age changes in the pharmacokinetics of paracetamol in neonates, infants and children"],"prefix":"10.1111","volume":"50","author":[{"given":"Brian J.","family":"Anderson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald A.","family":"Woollard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas H. G.","family":"Holford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,9,22]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1976193284"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.65.9.971"},{"key":"e_1_2_6_4_2","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1542\/peds.55.6.818","article-title":"Pharmacokinetics of acetaminophen in the human neonate; formation of acetaminophin glucuronide and sulfate in relation to plasma bilirubin concentration and d\u2010glucoric acid excretion","volume":"55","author":"Levy G","year":"1975","journal-title":"Pediatrics"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1159\/000457553"},{"key":"e_1_2_6_6_2","first-page":"376","article-title":"Paracetamol prescribing habits in a children's hospital","volume":"109","author":"Anderson B","year":"1996","journal-title":"N Z Med J"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199529050-00001"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.1995.tb00291.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1998.00780.x"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199902000-00014"},{"key":"e_1_2_6_11_2","volume-title":"NONMEM Users Guide","author":"Sheiner LB","year":"1979"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199630050-00001"},{"key":"e_1_2_6_13_2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1017\/CBO9780511608551","volume-title":"The ecological implications of body size, Chapter 4","author":"Peters HP","year":"1983"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0300-9629(80)90255-8"},{"key":"e_1_2_6_15_2","first-page":"153","volume-title":"Pharmacokinetic and pharmacodynamic data analysis","author":"Gabrielsson J","year":"1994"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1890\/03-0757"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1754.1993.tb00454.x"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(98)70476-7"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1992.tb03831.x"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)80307-5"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5420.1677"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1159\/000457538"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199733050-00001"},{"key":"e_1_2_6_24_2","volume-title":"Paracetamol (Acetaminophen) A Critical Bibliographic Review","author":"Prescott LF","year":"1996"},{"key":"e_1_2_6_25_2","first-page":"1233","article-title":"Characterization of an \u2018in vitro\u2019 blood\u2013brain barrier: effects of molecular size and lipophilicity on cerebrovascular endothelial transport rates of drugs","volume":"247","author":"Van Bree JB","year":"1988","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1985.tb03030.x"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.62.1.26"},{"key":"e_1_2_6_28_2","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/S0016-5085(76)80277-6","article-title":"Development of the human intestinal tract: a review","volume":"70","author":"Grand RJ","year":"1976","journal-title":"Gastroenterology"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198207020-00001"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1975.tb00568.x"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1754.1998.00267.x"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00607678"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199121020-00003"},{"key":"e_1_2_6_34_2","first-page":"89","article-title":"Absorption rate and bioavailability from fatty suppositories","volume":"112","author":"Moolenar F","year":"1979","journal-title":"Pharmaceutisch Weekblod Sci Edition"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00570165"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199708000-00010"},{"key":"e_1_2_6_37_2","first-page":"175","article-title":"Acetaminophen use in children: more is not better","volume":"130","author":"Heubi JE","year":"1997","journal-title":"J Pediatr"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1991.tb03873.x"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(98)70479-2"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(97)70359-7"},{"key":"e_1_2_6_41_2","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1093\/clinchem\/32.5.721","article-title":"Drug use in the neonate: interrelationships of pharmacokinetics, toxicity, and biochemical maturity","volume":"32","author":"Warner A","year":"1986","journal-title":"Clin Chem"},{"key":"e_1_2_6_42_2","first-page":"386","article-title":"Acetaminophen poisoning in infancy","volume":"137","author":"Greene JW","year":"1983","journal-title":"Am J Dis Child"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(96)90050-8"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2125.2000.00231.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2125.2000.00231.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1365-2125.2000.00231.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T16:50:35Z","timestamp":1698598235000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1046\/j.1365-2125.2000.00231.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,8]]},"references-count":42,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2000,8]]}},"alternative-id":["10.1046\/j.1365-2125.2000.00231.x"],"URL":"https:\/\/doi.org\/10.1046\/j.1365-2125.2000.00231.x","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,8]]}}}