title: Pharmacokinetics of tacrolimus (FK506) in paediatric liver transplant recipients.
abstract: The pharmacokinetics of intravenous and oral tacrolimus was assessed in paediatric liver transplant patients at two centers in Europe. Sixteen patients, age 0.7 to 13 years, participated in the study; 12 patients were evaluable for intravenous pharmacokinetics, and 16 for oral. Intravenous tacrolimus was given as a continuous 24 h infusion (mean 0.037+/-0.013 mg/kg/day), and oral tacrolimus was given in 2 doses per day (mean 0.152+/-0.015 mg/kg). Whole blood samples for the intravenous pharmacokinetic profile were taken before initiation of the first infusion, 4, 8, 12 and 24 h post-infusion, and every 24 h thereafter until intravenous administration was discontinued. During the 12 h wash-out period between intravenous and oral administration, samples were taken every 3 h. Samples for the oral pharmacokinetic profile were taken immediately before the first oral dose and 0.5, 0.75, 1, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-administration. Non-compartmental procedures were used to characterise the pharmacokinetic parameters. Mean estimates for clearance and terminal half-life were 2.3+/-1.2 ml/min/kg and 11.5+/-3.8 h, respectively, following intravenous tacrolimus. The mean bioavailability of oral tacrolimus was 25+/-20%. A strong correlation was observed between AUC and trough whole blood levels of tacrolimus (r=0.90). The clearance was approximately 2-fold higher than that previously observed in adults; this could explain the higher dosage requirements in children.
authors.affiliation: Service de Chirurgie Pediatrique, Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: P E
authors.initials: PE
authors.lastname: Wallemacq
authors.forename: V
authors.initials: V
authors.lastname: Furlan
authors.forename: A
authors.initials: A
authors.lastname: Möller
authors.forename: A
authors.initials: A
authors.lastname: Schäfer
authors.forename: P
authors.initials: P
authors.lastname: Stadler
authors.forename: I
authors.initials: I
authors.lastname: Firdaous
authors.forename: A M
authors.initials: AM
authors.lastname: Taburet
authors.forename: R
authors.initials: R
authors.lastname: Reding
authors.forename: S
authors.initials: S
authors.lastname: Clement De Clety
authors.forename: J
authors.initials: J
authors.lastname: De Ville De Goyet
authors.forename: E
authors.initials: E
authors.lastname: Sokal
authors.forename: L
authors.initials: L
authors.lastname: Lykavieris
authors.forename: V
authors.initials: V
authors.lastname: Van Leeuw
authors.forename: O
authors.initials: O
authors.lastname: Bernard
authors.forename: J B
authors.initials: JB
authors.lastname: Otte
authors.forename: N A
authors.initials: NA
authors.lastname: Undre
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007223:Infant; D007275:Injections, Intravenous; D016031:Liver Transplantation; D008297:Male; D010865:Pilot Projects; D013223:Statistics as Topic; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus