title: Measurement of blood concentrations of FK506 (tacrolimus) and its metabolites in seven liver graft patients after the first dose by h.p.l.c.-MS and microparticle enzyme immunoassay (MEIA).
abstract: 1. Blood and urine concentrations of the macrolide immunosuppressant FK506 and its metabolites were measured in seven orthotopic liver transplant patients after the first oral dose of FK506 (0.04 +/- 0.02 mg kg-1) used as primary immunosuppressant. A specific h.p.l.c.-MS assay was used, allowing the measurement of parent drug and eight metabolites. Results were compared with those obtained using a microparticle enzyme immunoassay (MEIA). 2. Blood drug concentrations were described by an open two compartment model with first-order absorption giving the following mean data: tmax: 1.9 (h), Cmax: 17.4 (microgram l-1), AUC: 328.1 (microgram l-1 h), t1/2,1: 0.74 (h). The terminal elimination half-life was estimated at about 26 h using the h.p.l.c.-MS assay. 3. The metabolites found in blood were demethyl-FK506 and demethyl-hydroxy-FK506, while in urine FK506 and eight of its metabolites were detected.
authors.affiliation: Institut für Allgemeine Pharmakologie, Medizinische Hochschule Hannover, Germany.
authors.forename: A K
authors.initials: AK
authors.lastname: Gonschior
authors.forename: U
authors.initials: U
authors.lastname: Christians
authors.forename: F
authors.initials: F
authors.lastname: Braun
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: D000328:Adult; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D007124:Immunoenzyme Techniques; D007677:Kidney Function Tests; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D013058:Mass Spectrometry; D008863:Microspheres; D008875:Middle Aged; D016559:Tacrolimus / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D016559:Tacrolimus