Pharmacokinetics of tacrolimus (FK506) in paediatric liver transplant recipients.
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.
Wallemacq
P E
PE
Service de Chirurgie Pediatrique, Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Furlan
V
V
Möller
A
A
Schäfer
A
A
Stadler
P
P
Firdaous
I
I
Taburet
A M
AM
Reding
R
R
Clement De Clety
S
S
De Ville De Goyet
J
J
Sokal
E
E
Lykavieris
L
L
Van Leeuw
V
V
Bernard
O
O
Otte
J B
JB
Undre
N A
NA
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
D007166:Immunosuppressive Agents; D016559:Tacrolimus