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

14 July 2014 : Original article  

The Pharmacokinetics of Everolimus in De Novo Kidney Transplant Patients Receiving Tacrolimus: An Analysis from the Randomized ASSET Study

Lionel RostaingABE, Maarten H.L. ChristiaansABE, John M. KovarikCE, Julio PascualABE

DOI: 10.12659/AOT.890673

Ann Transplant 2014; 19:337-345


BACKGROUND: Pharmacokinetic data regarding a drug-drug interaction between everolimus and tacrolimus are sparse.

MATERIAL AND METHODS: In a pharmacokinetic substudy of the randomized ASSET trial, 46 de novo kidney transplant patients receiving very low (1.5–3 ng/mL) or low (4–7 ng/mL) tacrolimus exposure after month 3, both with everolimus and steroids, provided area under the curve (AUC) concentration profiles at day 5 and months 1, 3, and 12.

RESULTS: At month 12, mean values for tacrolimus trough concentration (C0), peak concentration (Cmax), and AUC0–12 in the very low tacrolimus group were approximately half that in the low tacrolimus group, but everolimus dose, C0, Cmax, and AUC0–12 were virtually identical in both groups. In a cross-study comparison with data at months 1 and 3 from the pharmacokinetic substudy of the A2307 trial, in which patients received cyclosporine, mean values for everolimus C0, Cmax and AUC0–12 were similar to those in the ASSET trial but the everolimus dose needed to achieve similar exposure was 1.5- to 2-fold higher with concomitant tacrolimus versus cyclosporine.

CONCLUSIONS: Everolimus exposure is unaffected when tacrolimus exposure is down-titrated within the trough concentration range of 1.5–7 ng/mL. Higher doses of everolimus are needed to achieve a given exposure when combined with tacrolimus versus cyclosporine.

Keywords: Kidney Transplantation, Pharmacokinetics, Tacrolimus

Add Comment 0 Comments

1030 36

In Press

10 Nov 2023 : Original article  

Effects of Preservation of Donor Liver Gastroduodenal Artery on Post-Transplant Biliary Complications in 18...

Ann Transplant In Press; DOI:  

07 Nov 2023 : Original article  

Allogeneic Hematopoietic Stem Cell Transplantation Can Improve Prognosis of Extramedullary Infiltration Pos...

Ann Transplant In Press; DOI:  

06 Nov 2023 : Original article  

Clinical Outcomes of Administration of Rituximab for Desensitization in Liver Transplant Patients with Pref...

Ann Transplant In Press; DOI:  

06 Nov 2023 : Original article  

Short-Term Monitoring of Graft Regeneration in Partial Liver Transplantation Recipients

Ann Transplant In Press; DOI:  

Most Viewed Current Articles

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

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

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