Tacrolimus Therapeutic Response, Pharmacokinetics and Adherence in Liver Transplant Recipients

A high intra and interindividual pharmacokinetics variability characterize Tacrolimus. Data regarding factors influencing its pharmacokinetics and pharmacodynamics in liver transplantation are limited. This study aimed to assess tacrolimus therapeutic response, pharmacokinetics and adherence in liver transplant recipients. The study was conducted at the Clinical Pharmacology Department for 12 years, from January 2009 to March 2021. We included liver transplant patients treated with tacrolimus referred to our department for tacrolimus therapeutic drug monitoring. Secondly, we assessed tacrolimus adherence in liver transplant recipients using a prospective Morisky questionnaire. We included 894 tacrolimus trough concentration C<sub>0 </sub>from 76 patients. The mean age was 24.4 ± 10.2 years. The sex ratio M/F was 1.3. The median C<sub>0</sub> was 8.53 ± 4.7 ng/mL. In 48.2% of cases, the C<sub>0</sub> was in the therapeutic range. Children required higher weight doses of tacrolimus compared to adults. C<sub>0</sub> and C<sub>0</sub>/dose ratios of tacrolimus were higher in adults and in male patients. Bilirubinemia, polypharmacy, and adherence were weakly correlated with C<sub>0</sub>. Mycophenolate mofetil, prednisolone, mehylprednisolone, amphotericin B, fluconazole, and omeprazole were associated with increased tacrolimus C<sub>0</sub>, while irbesartan was associated with decreased tacrolimus C<sub>0</sub>. The intraindividual coefficient of variability (CV) ranged from 20.4 to 119%. The interindividual CV was 46.1%. The tacrolimus index of variability ranged from 1.6 to 15.1. Age greater than 18 years increased tacrolimus adherence by 3.892-fold in liver transplant patients. Tacrolimus bioavailability was higher in adults and men. Adherence increased by 3.892-fold in liver transplant adults.