The impact of ethnic miscegenation on tacrolimus clinical pharmacokinetics and therapeutic drug monitoring

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dc.contributor.authorFelipe, C. R.
dc.contributor.authorSilva, H. T.
dc.contributor.authorMachado, P. G.
dc.contributor.authorGarcia, R.
dc.contributor.authorMoreira, SRD
dc.contributor.authorPestana, J. O.
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T12:33:28Z
dc.date.available2016-01-24T12:33:28Z
dc.date.issued2002-08-01
dc.description.abstractThe impact of ethnic miscegenation on tacrolimus clinical pharmacokinetics and therapeutic drug monitoring. We sought to determine the influence of ethnic miscegenation on tacrolimus pharmacokinetics and trough concentrations during the first 6 months after transplantation.Methods: Tacrolimus concentrations were measured in blood samples obtained from 22 transplant recipients during the first week of transplant, within pharmacokinetic profiles, and throughout the first 6 months post-transplant, using the Pro Tac II ELISA method. Pharmacokinetic parameters and between- and within-subject blood concentration variability were compared stratifying the total population in two distinct ethnic groups of white (W) and non-white (NW) patients, according to a stringent criterion.Results: Between-subject variability in dose-adjusted concentrations during dosing interval varied from 38.8 to 69.5%. Compared with W patients, NW patients showed higher variability in blood tacrolimus concentrations during dosing interval (37.40 +/- 5.64 vs. 56.95 +/- 11.49, p < 0.001) and lower drug exposures (AUC: 229.4 +/- 55.5 vs. 66.9 +/- 67.1 ng x h/mL, p=0.036). the correlation coefficients (r(2)) between C-0, C-12 or C-max and AUC were 0.83, 0.91 and 0.5, respectively. An equation derived from early time concentrations (C-0, C-1.5 and C-4) accounted for 94% of the variability observed in AUC. Compared with W patients, a higher proportion of tacrolimus blood determinations during the first week were below 10 &nu;g/mL in NW patients (24% vs. 62%, p=0.028). Tacrolimus absorption increased from week 1-4 (1.1 +/- 0.53 vs. 1.73 +/- 0.97 &nu;g/mL/mg, p < 0.0001) but was still showed high between- (41.6-70.4%) and within-subject (18.2-32.5%) variability, regardless of ethnicity, after stabilization.Conclusion: Non-white patients show higher tacrolimus variability and lower drug exposures after transplantation compared with W patients. Therefore, higher initial tacrolimus doses and intensive monitoring are recommended when administering tacrolimus-based immunosupressive therapy to NW patients of this transplant population.en
dc.description.affiliationUniversidade Federal de São Paulo, Hosp Rim & Hipertensao, Div Nephrol, BR-04038002 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Hosp Rim & Hipertensao, Div Nephrol, BR-04038002 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent262-272
dc.identifierhttp://dx.doi.org/10.1034/j.1399-0012.2002.01103.x
dc.identifier.citationClinical Transplantation. Copenhagen: Blackwell Munksgaard, v. 16, n. 4, p. 262-272, 2002.
dc.identifier.doi10.1034/j.1399-0012.2002.01103.x
dc.identifier.issn0902-0063
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/26938
dc.identifier.wosWOS:000176572100004
dc.language.isoeng
dc.publisherBlackwell Munksgaard
dc.relation.ispartofClinical Transplantation
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectkidney transplanten
dc.subjectpharmacokineticen
dc.subjectraceen
dc.subjecttacrolimusen
dc.titleThe impact of ethnic miscegenation on tacrolimus clinical pharmacokinetics and therapeutic drug monitoringen
dc.typeinfo:eu-repo/semantics/article
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