{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:39:59Z","timestamp":1761100799757,"version":"build-2065373602"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:00:00Z","timestamp":1325808000000},"content-version":"vor","delay-in-days":2196,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:p><jats:bold>Study Objectives<\/jats:bold>. To compare the disposition of cyclosporine after the administration of two oral formulations to children undergoing hematopoietic stem cell transplantation, and to evaluate the relationship between whole blood cyclosporine concentrations during the dosing interval and the area under the whole blood concentration\u2010time curve.<\/jats:p><jats:p><jats:bold>Design<\/jats:bold>. Prospective, descriptive, crossover study.<\/jats:p><jats:p><jats:bold>Setting<\/jats:bold>. Hematopoietic stem cell transplantation unit in a tertiary\u2010quaternary university\u2010affiliated pediatric hospital.<\/jats:p><jats:p><jats:bold>Patients<\/jats:bold>. Twenty\u2010four pediatric patients aged 0.5\u201316.9 years undergoing allogeneic hematopoietic stem cell transplantation.<\/jats:p><jats:p><jats:bold>Intervention<\/jats:bold>. The modified oral formulation of cyclosporine was given on the first day (divided as two doses), and a single identical dose of the original oral formulation was given on the morning of the second day.<\/jats:p><jats:p><jats:bold>Measurements and Main Results<\/jats:bold>. Blood samples were obtained at 0, 0.5, 1.25, 2, 4, 6, 9, and 12 hours after the morning dose from the lumen of the central venous catheter not previously used for intravenous cyclosporine administration. Cyclosporine concentration\u2010time data were analyzed by using noncompartmental methods. Mean \u00b1 SD maximum concentrations were significantly higher after administration of the modified form than after administration of the original form (594.9 \u00b1 349.7 vs 483.0 \u00b1 363.0 \u03bcg\/L, p=0.003), as was the area under the concentration\u2010time curve from 0\u201312 hours (AUC<jats:sub>0\u201312<\/jats:sub>; 3432 \u00b1 1563 vs 3144 \u00b1 1780 \u03bcg\/L\u2022hr, p=0.022). For both formulations, cyclosporine concentrations at 4 hours after administration were most strongly correlated with the AUC<jats:sub>0\u201312<\/jats:sub>. Unlike that of the original formulation, the trough cyclosporine concentration of the modified form had the weakest relationship with AUC (Spearman \u03c1 coefficient 0.584, p=0.003).<\/jats:p><jats:p><jats:bold>Conclusion<\/jats:bold>. Cyclosporine absorption is lower in children undergoing hematopoietic stem cell transplantation than in children receiving solid organ transplants. Dosage adjustment for the modified formulation based on trough concentration may not be appropriate because its relationship with the AUC was weak. The link between pharmacokinetic parameters and clinical outcomes, such as graft\u2010versus\u2010host disease, must be further studied.<\/jats:p>","DOI":"10.1592\/phco.2006.26.1.15","type":"journal-article","created":{"date-parts":[[2006,1,3]],"date-time":"2006-01-03T12:30:53Z","timestamp":1136291453000},"page":"15-22","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Disposition of Two Oral Formulations of Cyclosporine in Pediatric Patients Receiving Hematopoietic Stem Cell Transplants"],"prefix":"10.1002","volume":"26","author":[{"given":"L. Lee","family":"Dupuis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracey","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. 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