{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:47:18Z","timestamp":1772160438333,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,6,6]],"date-time":"2007-06-06T00:00:00Z","timestamp":1181088000000},"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":[[2007,12]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To compare the pharmacokinetics of mycophenolic acid (MPA) and its metabolite (MPAG) when mycophenolate mofetil (MMF) is administered in combination with sirolimus or ciclosporin (CsA) in renal allograft recipients. Safety and efficacy (biopsy\u2010proven acute rejection (BPAR)) were also assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u2003=\u200345) were randomized 2\u2003:\u20031 to receive treatment with sirolimus (\n                      <jats:italic>n<\/jats:italic>\n                      \u2003=\u200330; dosed to maintain trough concentrations of 10\u201325\u2003ng\u2003ml\n                      <jats:sup>\u22121<\/jats:sup>\n                      until week 8, and then 8\u201315\u2003ng\u2003ml\n                      <jats:sup>\u22121<\/jats:sup>\n                      thereafter) or CsA (\n                      <jats:italic>n<\/jats:italic>\n                      \u2003=\u200315; administered as per centre practice) both in combination with daclizumab, oral MMF and corticosteroids. Pharmacokinetic assessments were performed at day 7, week 4, and months 3 and 6 post\u2010transplant. The primary endpoint was the AUC(0,12\u2003h) for MPA and MPAG. The pharmacokinetics of sirolimus were also assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MPA exposure was 39\u201350% lower (month 6 mean AUC(0,12\u2003h) (95%CI): 40.4 (33.8, 47.0)\n                      <jats:italic>vs.<\/jats:italic>\n                      68.5 (54.9, 82.0) \u00b5g\u2003ml\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u2003h) and MPAG exposure was 25\u201352% higher (722 (607, 838)\n                      <jats:italic>vs.<\/jats:italic>\n                      485 (402, 569) \u00b5g\u2003ml\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u2003h at month 6) in the presence of CsA compared with sirolimus across visits. BPAR was 40.0% with sirolimus and 13.3% with CsA. The incidence of hypertension, tremors and hirsutism was higher with CsA than with sirolimus, while the incidence of diarrhoea, hyperlipidaemia and impaired wound closure was higher with sirolimus. No deaths, malignancies or graft losses were reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Co\u2010administration of sirolimus with MMF led to greater MPA exposure, but lower MPAG exposure, than co\u2010administration with CsA. As rejection rates were higher in the absence of CsA, further study of calcineurin inhibitor\u2010free regimens is required before general recommendations can be made.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/j.1365-2125.2007.02934.x","type":"journal-article","created":{"date-parts":[[2007,6,6]],"date-time":"2007-06-06T19:47:10Z","timestamp":1181159230000},"page":"758-771","source":"Crossref","is-referenced-by-count":23,"title":["Pharmacokinetics, safety, and efficacy of mycophenolate mofetil in combination with sirolimus or ciclosporin in renal transplant patients"],"prefix":"10.1111","volume":"64","author":[{"given":"Mark D.","family":"Pescovitz","sequence":"first","affiliation":[]},{"given":"Flavio","family":"Vincenti","sequence":"additional","affiliation":[]},{"given":"Marquis","family":"Hart","sequence":"additional","affiliation":[]},{"given":"Larry","family":"Melton","sequence":"additional","affiliation":[]},{"given":"John","family":"Whelchel","sequence":"additional","affiliation":[]},{"given":"Shamkant","family":"Mulgaonkar","sequence":"additional","affiliation":[]},{"given":"Diane","family":"McKay","sequence":"additional","affiliation":[]},{"given":"Mimi","family":"Leung","sequence":"additional","affiliation":[]},{"given":"Elizabeth","family":"Calleja","sequence":"additional","affiliation":[]},{"given":"M. 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