Logo Annals of Transplantation Logo Annals of Transplantation Logo Annals of Transplantation

01 December 2007

In vivo hepatic CYP3A4 activity is significantly higher in tacrolimus treated vs cyclosporine treated renal transplant recipients

H. de Jonge, M. Naesens, K. Verbeke, Y. Vanrenterghem, D. R. Kuypers

Ann Transplant 2008; 13(1): 34-34 :: ID: 880189

Abstract

Background: CYP3A4/5 and p-glycoprotein (PGP) are the major determinants of tacrolimus (Tac) and cyclosporine (CsA) pharmacokinetics. Although these drugs inhibit CYP3A4/5 and PGP, little is known about the extent of inhibition in vivo. The aim of this study was to examine whether Tac and CsA differentially affect in vivo hepatic CYP3A4 activity in renal transplant recipients.
Material/Methods: The N-methyl-[sup]14[/sup] C-Erythromycine Breath Test (EBT) was performed in 12 Tac and 7 CsA treated renal transplant recipients at 1 (n=4) or 3 (n=15) months after transplantation. The cumulative amount of [sup]14[/sup]C-CO[sub]2[/sub] exhaled in one hour expressed as % of the administered dose [sup]14[/sup]C (EBT C[sub]60[/sub] [%]) reflects in vivo hepatic CYP3A4 activity.
Results: There were no significant differences in baseline characteristics (age, weight, time after transplantation, methylprednisolone dose, concomitant medication, creatinine, hematocrit, albumin), except for a significantly higher number of females in the Tac-group (Tac=6/12 vs CsA=0/7, p=0.04). EBT C[sub]60[/sub] was significantly higher in the Tac-group (median EBT C[sub]60[/sub] Tac=1.99% vs CsA=1.45%, p=0.004, Figure 1). Reanalysis excluding 1 month data (median EBT C[sub]60[/sub] Tac=1.99% vs CsA=1.45%, p=0.012) and female patients (median EBT C[sub]60[/sub] Tac=1.95% vs CsA=1.45%, p=0.018) showed similar results. In multivariate regression analysis (stepwise selection) Tac vs CsA was the only variable that was significantly associated with EBT C[sub]60[/sub] (R[sup]2[/sup]=0.38, p=0.005).
Conclusions: Renal transplant recipients treated with tacrolimus have a significantly higher in vivo hepatic CYP3A4 activity early after transplantation as compared to cyclosporine treated patients, indicating a more pronounced CYP3A4 inhibition in vivo by cyclosporine. This finding could be important in daily clinical practice as differences in drug-drug interactions can be expected.

Keywords: P-Glycoprotein, Tacrolimus, Cyclosporine

0 Comments

Most Viewed Current Articles

26 Jan 2022 : Review article  

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models

DOI :10.12659/AOT.934924

Ann Transplant 2022; 27:e934924

24 Aug 2021 : Review article  

Normothermic Machine Perfusion (NMP) of the Liver – Current Status and Future Perspectives

DOI :10.12659/AOT.931664

Ann Transplant 2021; 26:e931664

29 Dec 2021 : Original article  

Efficacy and Safety of Tacrolimus-Based Maintenance Regimens in De Novo Kidney Transplant Recipients: A Sys...

DOI :10.12659/AOT.933588

Ann Transplant 2021; 26:e933588

15 Mar 2022 : Case report  

Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...

DOI :10.12659/AOT.935860

Ann Transplant 2022; 27:e935860

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358