{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T20:04:37Z","timestamp":1790366677853,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,3,7]],"date-time":"2013-03-07T00:00:00Z","timestamp":1362614400000},"content-version":"vor","delay-in-days":1041,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:p>To improve cyclosporine dose individualization, the authors carried out a comprehensive analysis of the effects of clinical and genetic factors on cyclosporine pharmacokinetics in 176 children before and up to 16 years after renal transplantation. Pretransplantation test doses of cyclosporine were given intravenously and orally, followed by blood sampling for 24 hours. After transplantation, cyclosporine was quantified at trough, 2 hours postdose, or with dose\u2010interval curves. A 3\u2010compartment population pharmacokinetic model was used to describe the data. Cyclosporine oral bioavailability increased more than 1.5\u2010fold in the first month after transplantation, returning thereafter gradually to its initial value in 1 to 1.5 years. Moreover, older children receiving cyclosporine twice daily as the gelatin capsule microemulsion formulation had an about 1.25 to 1.3 times higher bioavailability than did the younger children receiving the liquid formulation thrice daily. In 91 children with genetic data after transplantation, patients carrying the NR1I2 g.\u201025385C\u2010g.\u201024381A\u2010g.\u2010205_\u2010200GAGAAG\u2010g.7635G\u2010g.8055C haplotype had about one\u2010tenth lower bioavailability, per allele, than did noncarriers (P = .039). The significance of the NR1I2 genotype warrants further study. In conclusion, by accounting for the effects of developmental factors (body weight), time after transplantation, and cyclosporine dosing frequency\/formulation, it may be possible to improve individualization of cyclosporine dosing in children.<\/jats:p>","DOI":"10.1177\/0091270009348223","type":"journal-article","created":{"date-parts":[[2010,1,28]],"date-time":"2010-01-28T03:21:26Z","timestamp":1264648886000},"page":"581-597","source":"Crossref","is-referenced-by-count":26,"title":["Long\u2010Term Changes in Cyclosporine Pharmacokinetics After Renal Transplantation in Children: Evidence for Saturable Presystemic Metabolism and Effect of<i>NR1I2<\/i>Polymorphism"],"prefix":"10.1002","volume":"50","author":[{"given":"Samuel","family":"Fanta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siv","family":"J\u00f6nsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats O.","family":"Karlsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikko","family":"Niemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christer","family":"Holmberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalle","family":"Hoppu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janne T.","family":"Backman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,7]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3046.2006.00577.x"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2004.01.091"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.sempedsurg.2006.03.005"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2008.02167.x"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.03510807"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007060662"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199732060-00004"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241020-00004"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2007.03003.x"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199630050-00001"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241090-00001"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/86882"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(88)80073-1"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.43.100901.140233"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e3282f3ef72"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-1345(03)00474-3"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199404000-00007"},{"issue":"2","key":"e_1_2_5_19_2","first-page":"481","article-title":"Different pharmacokinetics of cyclosporine A early and late after renal transplantation","volume":"20","author":"Wilms HW","year":"1988","journal-title":"Transplant Proc"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.59"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1991.tb03971.x"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00852828"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2005.04.005"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-2607(98)00067-4"},{"key":"e_1_2_5_25_2","volume-title":"Texts in Statistical Science","author":"Manly BFJ.","year":"1997"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-4541-9"},{"key":"e_1_2_5_27_2","unstructured":"KarlssonMO HolfordNH.A tutorial on visual predictive checks. 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