{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:18:49Z","timestamp":1789805929151,"version":"4.0.1"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2004,3,23]],"date-time":"2004-03-23T00:00:00Z","timestamp":1080000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To develop a population pharmacokinetic model for pyrimethamine (PYR) and sulfadoxine (SDX) in children with congenital toxoplasmosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Children were treated with PYR (1.25\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) and SDX (25\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) (Fansidar<jats:sup>\u00ae<\/jats:sup>) plus folinic acid (Lederfoline<jats:sup>\u00ae<\/jats:sup> 5\u2003mg). Plasma concentrations, available from a therapeutic drug monitoring database, were determined by high\u2010performance liquid chromatogrphy. Population pharmacokinetic analysis was performed using a nonlinear mixed effects model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eighty\u2010nine children, aged 1\u2003week to 14\u2003years and weighing 2.9\u201359\u2003kg, were available for evaluation. Both PYR and SDX concentration\u2010time profiles were best described by a one\u2010compartment open model. Volume of plasma distribution (<jats:italic>V<\/jats:italic>) and clearance (CL) were significantly related to body weight (BW) using an allometric function. Typical CL and <jats:italic>V<\/jats:italic> estimates (95% confidence interval), for a child weighing 11\u2003kg were 5.50 (5.28, 5.73)\u2003l\u2003day<jats:sup>\u22121<\/jats:sup> and 36 (33, 39)\u2003l for PYR and 0.26 (0.25, 0.27)\u2003l\u2003day<jats:sup>\u22121<\/jats:sup> and 2.1 (1.9, 2.3)\u2003l for SDX. For BW between 3.5 and 60\u2003kg, plasma half\u2010lives were predicted to vary from 4.0 to 5.2\u2003days for PYR, and from 5.0 to 7.5\u2003days for SDX.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study indicated that body weight influences PYR and SDX pharmacokinetics in children. To optimize PYR\/SDX combination treatment in congenital toxoplasmosis, short dosing intervals in very young low\u2010wight children are probably appropriate.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2004.02077.x","type":"journal-article","created":{"date-parts":[[2004,5,18]],"date-time":"2004-05-18T16:04:33Z","timestamp":1084896273000},"page":"735-741","source":"Crossref","is-referenced-by-count":28,"title":["Population pharmacokinetics of pyrimethamine and sulfadoxine in children with congenital toxoplasmosis"],"prefix":"10.1111","volume":"57","author":[{"given":"T.","family":"Trenque","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Villena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Chemla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Quereux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Leroux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Jaussaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"R\u00e9my","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Dupouy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Millart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.\u2010M.","family":"Pinon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Urien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,4,21]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/00365549850160963"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.3.763"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)90785-3"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.3928\/0090-4481-19940301-07"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/157.1.14"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.32.3.303"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(99)70224-3"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198802043180502"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(89)80660-2"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)12021-6"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00606671"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1989.tb05381.x"},{"key":"e_1_2_5_14_2","first-page":"115","article-title":"Plasma concentrations in pyrimethamine and sulfadoxine and evaluation of pharmacokinetic data by computerized curve fitting","volume":"60","author":"Weidekamm E","year":"1982","journal-title":"Bull World Health Organ"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.5.1040"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(90)90002-V"},{"key":"e_1_2_5_17_2","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1128\/jcm.34.3.579-583.1996","article-title":"Early neonatal diagnosis of congenital toxoplasmosis: value of comparative enzyme\u2010linked immunofiltration assay immunological profiles and anti\u2010Toxoplasma gondii immunoglobulin M (IgM) or IgA immunocapture and implications for postnatal therapeutic strategies","volume":"34","author":"Pinon JM","year":"1996","journal-title":"J Clin Microbiol"},{"key":"e_1_2_5_18_2","unstructured":"UrienS.MP2 (V 2.0)\u2014a windows application for population pharmacokinetics. 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