Premium
A randomized, crossover pharmacokinetic study comparing generic tacrolimus vs. the reference formulation in subpopulations of kidney transplant patients
Author(s) -
Bloom R. D.,
TrofeClark J.,
Wiland A.,
Alloway R. R.
Publication year - 2013
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.12256
Subject(s) - tacrolimus , medicine , pharmacokinetics , crossover study , urology , confidence interval , bioavailability , bioequivalence , pharmacology , gastroenterology , transplantation , placebo , alternative medicine , pathology
An exploratory, post hoc analysis was performed using data from a prospective, multicenter, open‐label, randomized, two‐period (14 d per period), two‐sequence, crossover, steady‐state pharmacokinetic study comparing generic tacrolimus ( S andoz) vs. reference tacrolimus in stable renal transplant patients receiving their pre‐study twice‐daily dose. Pharmacokinetic parameters were compared in 68 patients according to gender, A frican A merican ethnicity, the presence or absence of diabetes, and use of steroids. The ratios of tacrolimus AUC 0–12 h , C max , and C 12 with generic vs. reference tacrolimus were calculated using the geometric mean ( GM ) of dose‐normalized values at days 14 and 28. Mean ( SD ) tacrolimus dose at baseline was 5.7 (4.2) mg/d. There were no consistent differences in dose‐normalized AUC 0–12 h , C 12 , C max, or t max between the generic and reference preparations within subpopulations. The 90% confidence intervals ( CI ) for the ratios of dose‐normalized AUC 0–12 h and C 12 with generic vs. reference tacrolimus were within 80–125% for all subpopulations, as were 90% CI s for C max other than for females, A frican A mericans, and non‐diabetics, which is not unexpected given the wide variability of tacrolimus C max and the small subpopulation sizes. These exploratory results suggest that this generic tacrolimus preparation would be expected to offer comparable bioavailability to the reference drug in these patient subpopulations.