Pharmacokinetics of tacrolimus in pregnant solid organ transplant recipients: A retrospective study

Data on pharmacokinetics of tacrolimus during pregnancy is limited. Therefore, the aim of this retrospective study was to characterize the whole blood pharmacokinetics of tacrolimus throughout pregnancy. In this single-center retrospective cohort study whole blood tacrolimus trough concentrations (corrected for the dose; C/D ratios) were compared before, monthly during and after pregnancy in kidney, liver, and lung transplant recipients who became pregnant and gave birth between 2000 and 2022. Descriptive statistics and linear mixed models were used to characterize changes in tacrolimus C/D ratios before, during and after pregnancy. The total study population included 46 pregnancies (31 pregnant women). 19, 21, and 6 pregnancies were after kidney, liver and lung transplantation respectively. Immediate release or extended release formulation were used in 54.5% and 45.5% of the women, respectively. Tacrolimus C/D ratios significantly (P<0.001) decreased (-48%) compared to pre-pregnancy state at seven months pregnancy. These ratios recovered within 3 months postpartum (P = 0.002). C/D ratios tended to be lower during treatment with an extended release formulation than with an immediate release formulation (P = 0.071). Transplantation type did not significantly affect C/D ratios during pregnancy (P = 0.873). In conclusion, we found that tacrolimus whole blood pharmacokinetics change throughout pregnancy, with the lowest C/D ratios (-48% decrease) in the seventh month of pregnancy. In general, the decrease in C/D ratios seems to stabilize from month 4 onwards compared to pre-pregnancy.