{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:30:51Z","timestamp":1787506251344,"version":"build-2736575974"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Interventions"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>Sirolimus-eluting stents may have clinical advantages over bare-metal stents in the extremely proliferative environment of the neonatal arterial duct. However, sirolimus has immunosuppressive actions and little is known regarding sirolimus pharmacokinetics in the newborn.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>This is a retrospective review of sirolimus pharmacokinetics in neonates who underwent sirolimus-eluting stent implantation in the arterial duct for pulmonary blood flow augmentation. Pharmacokinetic parameters were obtained by noncompartmental analysis and by a Bayesian one-compartment nonlinear mixed model. Nine neonates received a single sirolimus-eluting stent with a total sirolimus dose of 245 \u03bcg (n=1), 194 \u03bcg (n=5), or 143 \u03bcg (n=3). Peak sirolimus concentrations were 13.6\u00b14.5 \u03bcg\/L (24.8 \u03bcg\/L highest) and clearance was 0.042\u00b10.03 L\/hour (noncompartmental analysis) and 0.051 L\/hour (95% credible intervals 0.037\u20130.069, nonlinear mixed model). Sirolimus remained &gt;5 \u03bcg\/L, the trough level used in oral immunosuppressive therapy, for (95% credible interval) 15.9 (11.4, 22.8), 12.9 (7.6, 19.0), and 8.4 (2.3, 14.5) days for the 245, 194, and 143 \u03bcg sirolimus dose stents, respectively. Estimates of the duration of systemic immunosuppression are provided for combinations of 2 stents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>In neonates after sirolimus-eluting stent implantation, peak sirolimus levels were 20\u00d7 higher and clearance 30\u00d7 lower than previously reported in older children and adults. Sirolimus levels were within the immunosuppressive range for a prolonged period, but with no observable clinically significant adverse outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circinterventions.114.002233","type":"journal-article","created":{"date-parts":[[2015,5,4]],"date-time":"2015-05-04T22:04:25Z","timestamp":1430777065000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Pharmacokinetics of Sirolimus-Eluting Stents Implanted in the Neonatal Arterial Duct"],"prefix":"10.1161","volume":"8","author":[{"given":"Kyong-Jin","family":"Lee","sequence":"first","affiliation":[{"name":"From The Labatt Family Heart Centre, Division of Cardiology (K.-J.L., L.B., R.R.C.) and the Department of Pharmacy (W.S.), The Hospital for Sick Children, University of Toronto School of Medicine, Toronto, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnie","family":"Seto","sequence":"additional","affiliation":[{"name":"From The Labatt Family Heart Centre, Division of Cardiology (K.-J.L., L.B., R.R.C.) and the Department of Pharmacy (W.S.), The Hospital for Sick Children, University of Toronto School of Medicine, Toronto, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Benson","sequence":"additional","affiliation":[{"name":"From The Labatt Family Heart Centre, Division of Cardiology (K.-J.L., L.B., R.R.C.) and the Department of Pharmacy (W.S.), The Hospital for Sick Children, University of Toronto School of Medicine, Toronto, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv R.","family":"Chaturvedi","sequence":"additional","affiliation":[{"name":"From The Labatt Family Heart Centre, Division of Cardiology (K.-J.L., L.B., R.R.C.) and the Department of Pharmacy (W.S.), The Hospital for Sick Children, University of Toronto School of Medicine, Toronto, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.03.066"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2007.123000"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/euhj.1998.0977"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0146-0005(96)80067-X"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.107.4.1007"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(200002)190:3<300::AID-PATH596>3.0.CO;2-I"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000163587.36485.A7"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)07751-6"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119038"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc3601.093987"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012843"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.737734"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ccd.20565"},{"key":"e_1_3_3_15_2","first-page":"329","article-title":"Placement of a sirolimus-coated stent in the distal left internal mammary artery of an 8-year-old boy.","volume":"17","author":"Rashid A","year":"2005","unstructured":"Rashid A, Ringewald J, Saucedo J. 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