Analysis of Pharmacokinetics of Tacrolimus during Allogeneic Hemopoietic Stem Cell Transplantation (Allo-SCT) and Use of Results in Study on Appropriate Usage

Abstract

Tacrolimus is an immunosuppressant which is usually administered to reduce the incidence of graft-versus-host-disease (GVHD) during allogeneic hemopoietic stem cell transplantation.The trough levels of tacrolimus are usually used as an index for monitoring pharmacokinetics and we conducted a pharmacokinetic analysis of the usefulness and validity of trough level monitoring following its oral administration.
The mean bioavailability of tacolimus in 19 subjects was 34±14.1%.There appeared to be a statistically significant correlation between trough levels and the area under the curve (AUC) (AUCpo (0-12)=15.46×trough level-8.64,R²=0.92),and this correlation seemed to be little influenced by subject background or drug-drug interaction.Using our results we made a table for the conversion of trough levels to AUC,since the immunosuppressive effect of tacrolimus was considered to be correlated with the AUC.
The conversion table will enable us to predict AUC values based on estimated target trough levels when switching the administration route from continuous instillation to oral administration,and will thus help ensure the appropriate use of tacrolimus in treatment.