EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS 1998, Vol. 23, No.3, pp. 367-370 Pharmacokinetics of tacrolimus (FK506) in paediatric liver transplant recipients 1 2·· 3 .. 3 3 P.E. WALLEMACQ ,V. FURLAN, A. MOLLER, A. SCHAFER, P. STADLER, I. FIRDAOUS 1 , A-M. TABURET 2 , R. REDING 1 , S. CLEMENT DE CLETy 1 , J. DE VILLE DE GOYET 1 , E. SOKAL I , L. LYKAVIERIS 1 , V. VAN LEEUW 1 , 2 1 3 O. BERNARD , J.B. OTTE and N.A. UNDRE 1 Service de Chirurgie Pediatrique, Universite Catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium 2Service d'Hepatologie, Hopital Kremlin-Bicetre, Paris, France 3Department of Pharmacokinetics, Fujisawa GmbH, Munich, Germany Receivedfor publication: June 9, 1997 Keywords: Tacrolimus, paediatric pharmacokinetics, pharmacokinetics SUMMARY 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 disconti- nued. 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/minlkg 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. INTRODUCTION Tacrolimus (FK506) is an established, well-tolerated, and potent primary immunosuppressant in paediatric Please send reprint requests to : Dr N.A. Undre, Fujisawa GmbH, Department of Pharmacokinetics, PO Box 800628, D-81606, Munich, Germany. liver transplantation (1,2). Studies comparing tacrolimus with cyclosporin have shown a reduced incidence of rejection in patients receiving tacrolimus therapy, a similar spectrum of side effects, and lower corticosteroid requirements (3,4). The pharmaco- kinetics of tacrolimus has been characterised in adult liver transplant recipients (5,6). This paper reports the pharmacokinetics of intravenous and oral tacrolimus