title: Pharmacokinetics of tacrolimus in kidney transplant recipients: twice daily versus once daily dosing.
abstract: Tacrolimus a macrolide immunosuppressant that is routinely given in two equally divided doses every 12 h. However, the time-dependent pharmacokinetics of tacrolimus suggest that once daily morning administration of tacrolimus may produce appropriate drug exposure. The purpose of this pilot study was to compare the pharmacokinetics and safety of twice vs. once daily administration of tacrolimus in stable kidney transplant recipients. Steady-state tacrolimus pharmacokinetic parameters were estimated on two occasions in an open-label, three-arm, two-period sequential study: twice daily dosing (Phase I) and once daily dosing (Phase II). In phase II, 18 patients were assigned to one of three arms: those taking 67%, 85% and 100% of their total twice daily dose once in the morning. In phase I, the mean area under the blood concentration-time curve (AUC) was higher after the morning dose, AUC(0-12) 117 +/- 40 vs. AUC(12-24) 97 +/- 30 ng/h/mL, p=0.012. In the 85% Group, the mean AUC ratio between twice and once daily was 1.0 (95% CI, 0.9-1.1) which predicted the best conversion ratio. Tacrolimus given once daily in the morning, at 85% of the twice daily dose, provides safe and equivalent drug exposure to twice daily dosing. This convenient dosing schedule may help to increase compliance and lower costs.
authors.affiliation: Department of Pharmacy, Barnes-Jewish Hospital at Washington University, St. Louis, MO, USA. klh2562@bjc.org
authors.forename: Karen L
authors.initials: KL
authors.lastname: Hardinger
authors.forename: Jeong M
authors.initials: JM
authors.lastname: Park
authors.forename: Mark A
authors.initials: MA
authors.lastname: Schnitzler
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Koch
authors.forename: Brent W
authors.initials: BW
authors.lastname: Miller
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Brennan
mesh_terms: D000328:Adult; D019540:Area Under Curve; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus