Tacrolimus exposure during pregnancy in kidney and liver transplantation recipients: A comparison between whole blood and plasma concentration-to-dose ratios

AIM: Tacrolimus monitoring is generally performed in whole blood (WB). Most (>85%) of circulating tacrolimus is bound to red blood cells. During pregnancy, WB monitoring might be suboptimal because of physiological changes including increased plasma volume and decreased haematocrit. Therefore, plasma tacrolimus monitoring might better indicate potential dosage needs in pregnant women.

METHODS: This prospective single-centre cohort study aimed to assess and compare tacrolimus WB and plasma concentration-to-dose (C/D) ratios before, during, and after pregnancy in kidney or liver transplant recipients. Linear mixed model analysis was used.

RESULTS: Nine women with 10 pregnancies were included. Based on WB tacrolimus concentrations, the median prescribed dosage significantly increased from 3 pre-pregnancy to 7.5 mg/day (+150%) in the third trimester (p < .001). The correlation between plasma and WB tacrolimus concentrations decreased throughout pregnancy with a correlation coefficient of 0.70 in the first trimester, 0.41 in the second and 0.30 in the third trimester of pregnancy. Median WB tacrolimus C/D ratios significantly decreased from 1.48 pre-pregnancy to 0.58 in the second and third trimester (-61%) (overall time effect p < .001). The effect of time became non-significant after adjusting for haematocrit (p = .40). Median plasma tacrolimus C/D ratios decreased from 0.03 pre-pregnancy to 0.02 in the first trimester (-33%) and remained stable afterward (overall time effect p = 0.33) and was not affected by haematocrit.

CONCLUSION: Our findings suggest that increasing dosages targeting WB tacrolimus concentrations may not be necessary during pregnancy based on plasma tacrolimus concentrations. However, larger studies are needed to confirm the findings.