OBJECTIVE: The aim of this study was to (a) quantify the gene expression of some cytochromes P(450) (CYP), especially CYP3A4, in serial biopsies from liver grafts the first year after orthoptic liver transplantation (OLT) and (b) study the relationship between hepatic CYP3A4 gene expression and plasma levels of cyclosporine and tacrolimus. METHODS: Liver tissue was obtained from surplus material of routine liver biopsies performed in 20 patients during the first year after OLT. Real-time reverse-transcription polymerase chain reaction was used for quantitative analyses of mRNA specific for CYP3A4, CYP3A5, CYP2E1 and CYP1A2 cytochromes as well as P-glycoprotein (P-gp). The gene expression of beta-actin was used as an internal standard for comparisons between samples. RESULTS: The median value of the mRNA for all cytochromes, but not for P-gp, was found to increase significantly over time. The gene expression of CYP3A5, CYP2E1 and CYP1A2 was higher than that of CYP3A4. The gene expression of CYP3A4 was related to the plasma concentration of cyclosporine and tacrolimus, i.e. low mRNA concentrations corresponded to high serum concentration levels and vice versa. The serum concentration of bilirubin or the prothrombin index did not correlate with the gene expression level of the cytochromes. CONCLUSION: The hepatic mRNA expression of CYP3A4 and the other investigated cytochromes increased during the first year after OLT. This was not the case with P-gp. Low CYP3A4 gene expression was related to high plasma levels of cyclosporine and tacrolimus and vice versa.
OBJECTIVE: The aim of this study was to (a) quantify the gene expression of some cytochromes P(450) (CYP), especially CYP3A4, in serial biopsies from liver grafts the first year after orthoptic liver transplantation (OLT) and (b) study the relationship between hepatic CYP3A4 gene expression and plasma levels of cyclosporine and tacrolimus. METHODS: Liver tissue was obtained from surplus material of routine liver biopsies performed in 20 patients during the first year after OLT. Real-time reverse-transcription polymerase chain reaction was used for quantitative analyses of mRNA specific for CYP3A4, CYP3A5, CYP2E1 and CYP1A2 cytochromes as well as P-glycoprotein (P-gp). The gene expression of beta-actin was used as an internal standard for comparisons between samples. RESULTS: The median value of the mRNA for all cytochromes, but not for P-gp, was found to increase significantly over time. The gene expression of CYP3A5, CYP2E1 and CYP1A2 was higher than that of CYP3A4. The gene expression of CYP3A4 was related to the plasma concentration of cyclosporine and tacrolimus, i.e. low mRNA concentrations corresponded to high serum concentration levels and vice versa. The serum concentration of bilirubin or the prothrombin index did not correlate with the gene expression level of the cytochromes. CONCLUSION: The hepatic mRNA expression of CYP3A4 and the other investigated cytochromes increased during the first year after OLT. This was not the case with P-gp. Low CYP3A4 gene expression was related to high plasma levels of cyclosporine and tacrolimus and vice versa.
Authors: T Aoyama; S Yamano; D J Waxman; D P Lapenson; U A Meyer; V Fischer; R Tyndale; T Inaba; W Kalow; H V Gelboin Journal: J Biol Chem Date: 1989-06-25 Impact factor: 5.157
Authors: K S Lown; R R Mayo; A B Leichtman; H L Hsiao; D K Turgeon; P Schmiedlin-Ren; M B Brown; W Guo; S J Rossi; L Z Benet; P B Watkins Journal: Clin Pharmacol Ther Date: 1997-09 Impact factor: 6.875
Authors: Ina Koch; Regina Weil; Renzo Wolbold; Jürgen Brockmöller; Elisabeth Hustert; Oliver Burk; Andreas Nuessler; Peter Neuhaus; Michel Eichelbaum; Ulrich Zanger; Leszek Wojnowski Journal: Drug Metab Dispos Date: 2002-10 Impact factor: 3.922
Authors: D R Nelson; L Koymans; T Kamataki; J J Stegeman; R Feyereisen; D J Waxman; M R Waterman; O Gotoh; M J Coon; R W Estabrook; I C Gunsalus; D W Nebert Journal: Pharmacogenetics Date: 1996-02