title: Tacrolimus (FK506) metabolite patterns in blood from liver and kidney transplant patients.
abstract: The metabolite patterns of tacrolimus in blood were evaluated in 41 kidney and liver graft recipients. Trough concentrations of tacrolimus and its metabolites were measured by HPLC-mass spectrometry and microparticle enzyme immunoassay in parallel. A statistically significant correlation between results of both assays was observed for kidney and liver transplant patients (r = 0.77, P <0.001 and r = 0.71, P <0.001, respectively). The main metabolites in blood were demethyl, demethylhydroxy, didemethyl, didemethylhydroxy, and hydroxy tacrolimus. These metabolites added up to 42% (range 0-145%) of the tacrolimus concentration in liver transplant patients and to 44.8% (range 16-152%) in kidney transplant patients. During episodes of impaired liver function, concentrations of tacrolimus and its metabolites were increased compared with normal liver function, indicating accumulation of metabolites, in particular second-generation metabolites such as didemethyl and didemethylhydroxy tacrolimus. Stepwise regression analysis including tacrolimus, its metabolites, and liver function parameters suggested a model including serum activities of gamma-glutamyltransferase, alkaline phosphatase, and alanine aminotransferase as predictors for increased concentrations of demethyl tacrolimus, didemethyl tacrolimus, and the parent drug.
authors.affiliation: Institut fur Allgemeine Pharmakologie, Hannover, Germany.
authors.forename: A K
authors.initials: AK
authors.lastname: Gonschior
authors.forename: U
authors.initials: U
authors.lastname: Christians
authors.forename: M
authors.initials: M
authors.lastname: Winkler
authors.forename: A
authors.initials: A
authors.lastname: Linck
authors.forename: J
authors.initials: J
authors.lastname: Baumann
authors.forename: K F
authors.initials: KF
authors.lastname: Sewing
mesh_terms: D000293:Adolescent; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D016559:Tacrolimus / Q000097:blood*
chemical_list: D016559:Tacrolimus