Tacrolimus pharmacokinetic drug interactions: effect of prednisone, mycophenolic acid or sirolimus

dc.contributor.authorPark, Sung-In [UNIFESP]
dc.contributor.authorFelipe, Claudia R. [UNIFESP]
dc.contributor.authorPinheiro-Machado, Paula G. [UNIFESP]
dc.contributor.authorGarcia, Riberto [UNIFESP]
dc.contributor.authorFernandes, Fernanda B. [UNIFESP]
dc.contributor.authorCasarini, Dulce E. [UNIFESP]
dc.contributor.authorTedesco-Silva, Helio [UNIFESP]
dc.contributor.authorMedina-Pestana, Jose O. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T13:52:16Z
dc.date.available2016-01-24T13:52:16Z
dc.date.issued2009-02-01
dc.description.abstractThis study was conducted to evaluate time-dependent pharmacokinetic changes and drug interactions over the first 6 months after transplantation in kidney transplant recipients receiving tacrolimus (TAC), prednisone (PRED) and mycophenolate mofetil (MMF) or sirolimus (SRL). Pharmacokinetic assessments were carried out at day 7 and months 1, 3, and 6 in kidney transplant recipients receiving TAC plus PRED with either MMF (2 g/day, n = 13) or SRL (15 mg loading dose, 5 mg for 7 days followed by 2 mg/day, n = 12). There were no differences in the main demographic characteristics or in mean PRED doses during the first 6 months after transplant. From day 7 to month 6, there was a 65% increase in TAC dose corrected exposure (dose corrected area under the curve; AUC) in patients receiving MMF (P = 0.005) and a 59% increase in TAC dose corrected exposure in patients receiving SRL (P = 0.008). From day 7 to month 6, there was a 72% increase in mycophenolate dose corrected exposure (P = 0.001) and a 65% increase in SRL dose corrected exposure (P = 0.008). TAC dose corrected exposure was 23% lower in patients receiving SRL compared with MMF (P = 0.012) on average over the study period. PRED dose reduction was associated with increase in TAC (in patients receiving SRL, P = 0.040) and mycophenolic acid (MPA) (P = 0.070) drug exposures. Tercile distribution of TAC drug exposure showed a positive correlation with mean SRL exposures (P = 0.016). Conversely, tercile distribution of SRL drug exposure showed a positive correlation with mean TAC exposures (P = 0.004). Time-dependent increases in TAC, MPA and SRL drug exposures occur up to 6 months after transplantation. Drug-to-drug interactions indicate that intense therapeutic drug monitoring is required to avoid under-or over-immunosuppression.en
dc.description.affiliationUniversidade Federal de São Paulo, Div Nephrol, Hosp Rim & Hipertensao, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Div Nephrol, Hosp Rim & Hipertensao, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent137-145
dc.identifierhttp://dx.doi.org/10.1111/j.1472-8206.2008.00644.x
dc.identifier.citationFundamental & Clinical Pharmacology. Malden: Wiley-Blackwell Publishing, Inc, v. 23, n. 1, p. 137-145, 2009.
dc.identifier.doi10.1111/j.1472-8206.2008.00644.x
dc.identifier.issn0767-3981
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/31309
dc.identifier.wosWOS:000264373100015
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofFundamental & Clinical Pharmacology
dc.rightsAcesso restrito
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectdrug interactionen
dc.subjectkidney transplantationen
dc.subjectmycophenolate mofetilen
dc.subjectpharmacokineticsen
dc.subjectprednisoneen
dc.subjectsirolimusen
dc.subjecttacrolimusen
dc.titleTacrolimus pharmacokinetic drug interactions: effect of prednisone, mycophenolic acid or sirolimusen
dc.typeArtigo
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