The Challenge of Achieving Target Drug Concentrations in Clinical Trials: Experience From the Symphony Study

Página do item simplificado
dc.contributor.authorEkberg, Henrik
dc.contributor.authorMamelok, Richard D.
dc.contributor.authorPearson, Thomas C.
dc.contributor.authorVincenti, Flavio
dc.contributor.authorTedesco-Silva, Helio [UNIFESP]
dc.contributor.authorDaloze, Pierre
dc.contributor.institutionLund Univ
dc.contributor.institutionMamelok Consulting
dc.contributor.institutionEmory Univ
dc.contributor.institutionUniv Calif San Francisco
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionCHUM Montreal
dc.date.accessioned2016-01-24T13:52:33Z
dc.date.available2016-01-24T13:52:33Z
dc.date.issued2009-05-15
dc.description.abstractBackground. the Symphony study compared four immunosuppressant regimens, defined by protocol-specified target drug concentrations. This subanalysis examines actual drug levels and the implications on the interpretation of results.Methods. de novo renal transplant patients (n = 1645) were randomized to receive mycophenolate mofetil (2 g/day) and corticosteroids in combination with standard-dose cyclosporine A (CsA; 150-300 ng/mL for 3 months then 100-200 ng/mL), or daclizumab induction and low-dose CsA (50-100 ng/mL), low-dose tacrolimus (Tac; 3-7 ng/mL), or low-dose sirolimus (SRL; 4-8 ng/mL).Results. Low-dose Tac was significantly superior for renal function, acute rejection, and graft survival at 12 months. Median trough levels of CsA, Tac, or SRL were toward the high end of target ranges in all groups, and 50% to 60% were within target. During weeks 1 to 8, only 6.5% to 11.0% of patients were consistently within target. At week 8, the range of concentrations encompassing 75% of patients on standard-dose CsA was 141 to 321 ng/mL; for low-dose CsA, 62 to 159 ng/mL; for low-dose Tac, 4.3 to 10.0 ng/mL, and for low-dose SRL, 4.4 to 11.2 ng/mL. the protocol-de fined target levels were approximately, but not fully achieved.Conclusions. To replicate the Symphony study results in clinical practice, the protocol-defined drug concentration targets should be aimed for, but the concentrations actually achieved may be regarded as acceptable. Future clinical studies should include measures of how well target drug levels were achieved to better guide further attempts to develop new regimens designed to reduce or eliminate calcineurin inhibitors.en
dc.description.affiliationLund Univ, Univ Hosp, Dept Nephrol & Transplantat, S-20502 Malmo, Sweden
dc.description.affiliationMamelok Consulting, Palo Alto, CA USA
dc.description.affiliationEmory Univ, Sch Med, Dept Surg, Emory Transplant Ctr, Atlanta, GA 30322 USA
dc.description.affiliationUniv Calif San Francisco, Moffitt Hosp, Transplant Serv, San Francisco, CA USA
dc.description.affiliationUniversidade Federal de São Paulo, Div Nephrol, Hosp Rim & Hipertensao, São Paulo, Brazil
dc.description.affiliationCHUM Montreal, Notre Dame Hosp, Dept Surg, Quebec City, PQ, Canada
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Div Nephrol, Hosp Rim & Hipertensao, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipF. Hoffmann-La Roche Ltd, Basel, Switzerland.
dc.format.extent1360-1366
dc.identifierhttp://dx.doi.org/10.1097/TP.0b013e3181a23cb2
dc.identifier.citationTransplantation. Philadelphia: Lippincott Williams & Wilkins, v. 87, n. 9, p. 1360-1366, 2009.
dc.identifier.doi10.1097/TP.0b013e3181a23cb2
dc.identifier.issn0041-1337
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/31522
dc.identifier.wosWOS:000266048100015
dc.language.isoeng
dc.publisherLippincott Williams & Wilkins
dc.relation.ispartofTransplantation
dc.rightsAcesso restrito
dc.subjectCalcinuerin inhibitorsen
dc.subjectMycophenolate mofetilen
dc.subjectTarget drug concentrationen
dc.titleThe Challenge of Achieving Target Drug Concentrations in Clinical Trials: Experience From the Symphony Studyen
dc.typeArtigo
Arquivos
Coleções
EPM - Artigos