Therapeutic Drug Monitoring of Tacrolimus-Personalized Therapy in Heart Transplantation: New Strategies and Preliminary Results in Endomyocardial Biopsies

Pharmaceutics

Monica Concardi¹  Eloisa Arbustini¹  Elisa Novello²  Simona De Gregori²  Riccardo Albertini²  Barbara Cattadori³  Annalisa De Silvestri⁴  Andrea Rapagnani⁵  Carlo Pellegrini⁶ 

[1] Centro Malattie Genetiche Cardiovascolari, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;U.O.C Laboratorio Analisi Chimico Cliniche, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;U.O.C. di Cardiochirurgia, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;U.O.S Epidemiologia Clinica e Biostatistica, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;Unità di Chirurgia Cardiaca, Dipartimento di Scienze Clinico Chirurgiche, Diagnostiche e Pediatriche, Università degli Studi di Pavia, 27100 Pavia, Italy;Unità di Chirurgia Cardiaca, Dipartimento di Scienze Clinico Chirurgiche, Diagnostiche e Pediatriche, Università degli Studi di Pavia—U.O.C. di Cardiochirurgia, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;

关键词: heart transplantation;    acute rejection;    therapeutic drug monitoring;    tacrolimus;    endomyocardial biopsies;   

DOI  :  10.3390/pharmaceutics14061247

来源: DOAJ

【 摘 要 】

Tacrolimus (TAC) is an immunosuppressant drug approved both in the US and in the EU, widely used for the prophylaxis of organ rejection after transplantation. This is a critical dose drug: low levels in whole blood can lead to low exposure and a high risk of acute rejection, whereas overexposure puts patients at risk for toxicity and infection. Both situations can occur at whole-blood concentrations considered to be within the narrow TAC therapeutic range. We assumed a poor correlation between TAC trough concentrations in whole blood and the incidence of acute rejection; therefore, we propose to study TAC concentrations in endomyocardial biopsies (EMBs). We analyzed 70 EMBs from 18 transplant recipients at five scheduled follow-up visits during the first year post-transplant when closer TAC monitoring is mandatory. We observed five episodes of acute rejection (grade 2R) in three patients (2 episodes at 0.5 months, 2 at 3 months, and 1 at 12 months), when TAC concentrations in EMBs were low (63; 62; 59; 31; 44 pg/mg, respectively), whereas concentrations in whole blood were correct. Our results are preliminary and further studies are needed to confirm the importance of this new strategy to prevent acute rejection episodes.

【 授权许可】

Unknown