title: A randomized pharmacokinetic study of generic tacrolimus versus reference tacrolimus in kidney transplant recipients.
abstract: Pharmacokinetic analyses comparing generic tacrolimus preparations versus the reference drug in kidney transplant patients are lacking. A prospective, multicenter, open-label, randomized, two-period (14 days per period), two-sequence, crossover and steady-state pharmacokinetic study was undertaken to compare twice-daily generic tacrolimus (Sandoz) versus reference tacrolimus (Prograf®) in stable renal transplant patients. AUC(0-12h)  and peak concentration (C(max) ) were calculated from 12 h pharmacokinetic profiles at the end of each period (days 14 and 28). Of 71 patients enrolled, 68 provided evaluable pharmacokinetic data. The ratios of geometric means were 1.02 (90% CI 97-108%, p = 0.486) for AUC(0-12h)  and 1.09 (90% CI 101-118%, p = 0.057) for C(max) . Mean (SD) C(0)  was 7.3(1.8) ng/mL for generic tacrolimus versus 7.0(2.1) ng/mL for reference tacrolimus based on data from days 14 and 28. Correlations between 12 h trough levels and AUC were r = 0.917 for generic tacrolimus and r = 0.887 for reference drug at day 28. These data indicate that generic tacrolimus (Sandoz) has a similar pharmacokinetic profile to the reference drug and is bioequivalent in kidney transplant recipients according to US Food and Drug Administration and European Medicines Agency guidelines.
authors: Division of Nephrology, Section of Transplantation, University of Cincinnati, Cincinnati, OH, USA. allowarr@ucmail.uc.edu
authors: R R
authors: RR
authors: Alloway
authors: B
authors: B
authors: Sadaka
authors: J
authors: J
authors: Trofe-Clark
authors: A
authors: A
authors: Wiland
authors: R D
authors: RD
authors: Bloom
mesh_terms: D019540:Area Under Curve; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D011446:Prospective Studies; D016559:Tacrolimus / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus