Conversion from cyclosporin A to tacrolimus in pediatric liver transplantation Furlan V, Debray D, Fourre C, Taburet A-M. Conversion from cyclosporin A to tacrolimus in pediatric liver transplantation. Pediatr Transplantation 2000: 4: 207±210. # Munksgaard, 2000 Abstract: The dosing regimen for conversion from cyclosporin A (CsA) to tacrolimus immunosuppression was studied in 12 pediatric liver allograft recipients. Patients were strati®ed according to their age. Tacrolimus was started orally at a dosage of 0.05 mg/kg b.i.d., 12 h after stopping CsA administration and increased thereafter if needed. Tacrolimus and CsA concentrations were assayed by immunoassay using, respectively, an IMx and a TDx autoanalyzer (Abbott-France). Mean CsA concentration was in the therapeutic range 12 h prior to and at the time of introduction of tacrolimus. After 72 h of tacrolimus therapy, CsA concentrations were undetectable whereas mean tacrolimus concentration was 10.4 ng/mL with a mean dose of 0.09 mg/ kg b.i.d. The decline of CsA concentration was clearly biphasic. A slower decline in CsA concentration was detected after initiation of tacrolimus therapy, suggesting an inhibition of CsA metabolism by tacrolimus. No nephrotoxicity was observed. This dosage regimen allowed effective immunosuppression while avoiding additive nephrotoxicity. Vale  rie Furlan 1 , Dominique Debray 2 , Catherine Fourre 3 and Anne-Marie Taburet 1 1 Department of Clinical Pharmacy, 2 Department of Pediatric Hepatology and 3 Immunoassay Laboratory, Bice Ãtre Hospital, Le Kremlin-Bice Ãtre, France Key words: tacrolimus ± cyclosporin A ± children ± liver transplantation Vale Ârie Furlan, Bice Ãtre Hospital, Department of Clinical Pharmacy, 78, rue du Ge Âne  ral Leclerc, 94275 Le Kremlin-Bice Ãtre Cedex, France Tel.:+33 1-4521-2964 Fax:+33 1-4521-2860 Accepted for publication: 27 January 2000 Tacrolimus (Prograf 1 , Fujisawa GmbH, Mu È nchen, Germany) is an immunosuppressive agent now commonly used as rescue therapy for rejecting liver allograft recipients failing conven- tional immunosuppression with CsA. Tacrolimus and CsA are both eliminated by biotransforma- tion mainly by CYP3A4 (1, 2). Metabolism of tacrolimus depends on liver function and patients with liver graft rejection are at greater risk of experiencing adverse effects related to ¯uctua- tions in blood concentrations of tacrolimus (3, 4). Moreover, in vitro studies have shown that tacrolimus is an inhibitor of CsA metabolism (5, 6). Therefore, conversion from CsA to tacrolimus needs to be carefully monitored. This study was designed to demonstrate whether tacrolimus impairs CsA disposition and to evaluate a dosing regimen for conversion from CsA to tacrolimus immunosuppression in pedia- tric liver allograft recipients. Patients and methods Twelve pediatric liver allograft recipients who were converted from CsA to tacrolimus within 15 days to 8 years post-transplantation, were included in this study. The group comprised seven boys and ®ve girls (age range 0.6±17 yr). Indications for tacrolimus therapy were steroid- resistant acute rejection in eight children, early stage chronic rejection (bile duct damage or bile duct loss limited to less than 50% of triads) in one, and later-stage chronic rejection (bile duct loss in more than 50% of triads) in three. Oral or intravenous CsA (Sandimmune 1 , Novartis, Basle, Switzerland) was discontinued 12 h prior to initiation of tacrolimus therapy. Tacrolimus was started orally at a dosage of 0.05 mg/kg b.i.d., and doses were then adjusted to maintain a blood trough concentration within 5±15 ng/mL (7). During the ®rst week following conversion, tacrolimus trough concentration was assayed daily using an immunoassay method with an IMx autoanalyzer (Abbott-France, Rungis, France) (8). Response to tacrolimus therapy was monitored using liver function tests. Abbreviations: b.i.d., twice daily administration; CsA, cyclosporin A; CYP3A4, cytochrome P450 3A4. Pediatr Transplantation 2000: 4: 207±210 Printed in UK. All rights reserved Copyright # Munksgaard 2000 Pediatric Transplantation ISSN 1397±3142 207