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Review
. 2013 Apr 15;95(7):908-15.
doi: 10.1097/TP.0b013e318278d367.

Interpreting tacrolimus concentrations during pregnancy and postpartum

Mary F Hebert  1 , Songmao Zheng, Karen Hays, Danny D Shen, Connie L Davis, Jason G Umans, Menachem Miodovnik, Kenneth E Thummel, Thomas R Easterling
Affiliations
Review

Interpreting tacrolimus concentrations during pregnancy and postpartum

Mary F Hebert et al. Transplantation. .

Abstract

Pregnancy after solid organ transplantation, although considered high risk for maternal, fetal, and neonatal complications, has been quite successful. Tacrolimus pharmacokinetic changes during pregnancy make interpretation of whole blood trough concentrations particularly challenging. There are multiple factors that can increase the fraction of unbound tacrolimus, including but not limited to low albumin concentration and low red blood cell count. The clinical titration of dosage to maintain whole blood tacrolimus trough concentrations in the usual therapeutic range can lead to elevated unbound concentrations and possibly toxicity in pregnant women with anemia and hypoalbuminemia. Measurement of plasma or unbound tacrolimus concentrations for pregnant women might better reflect the active form of the drug, although these are technically challenging and often unavailable in usual clinical practice. Tacrolimus crosses the placenta with in utero exposure being approximately 71% of maternal blood concentrations. The lower fetal blood concentrations are likely due to active efflux transport of tacrolimus from the fetus toward the mother by placental P-glycoprotein. To date, tacrolimus has not been linked to congenital malformations but can cause reversible nephrotoxicity and hyperkalemia in the newborn. In contrast, very small amounts of tacrolimus are excreted in the breast milk and are unlikely to elicit adverse effects in the nursing infant.

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Conflict of interest statement

Conflicts of interest:

No conflict of interest

Figures

Figure 1
Figure 1
Depicts a theoretical representation of tacrolimus distribution in blood of patients with A. normal red blood cell count and normal albumin, B. anemia and normal albumin, C. normal red blood cell count and hypoalbuminemia and D. anemia and hypoalbuminemia.
Figure 2
Figure 2
A. Average (± SD), dose-normalized (1 mg/day), whole blood tacrolimus trough concentrations during early-, mid-, and late-pregnancy as well as > 3 months postpartum. B. Average (± SD) tacrolimus dose (mg/day) during early-, mid-, and late-pregnancy as well as > 3 months postpartum. C. Average (± SD) whole blood tacrolimus trough concentrations during early-, mid-, and late-pregnancy as well as > 3 months postpartum. D. Average (± SD) unbound tacrolimus trough concentrations during early-, mid-, and late-pregnancy as well as > 3 months postpartum.
Figure 3
Figure 3
Correlations between serum creatinine concentrations during pregnancy and postpartum and A. blood, B. plasma and C. unbound tacrolimus trough concentrations in non-rejecting transplantation recipients
See this image and copyright information in PMC

References

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