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Interpreting Tacrolimus Concentrations During Pregnancy and Postpartum.
MedLine Citation:
PMID:  23274970     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Mary F Hebert; Songmao Zheng; Karen Hays; Danny D Shen; Connie L Davis; Jason G Umans; Menachem Miodovnik; Kenneth E Thummel; Thomas R Easterling
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-28
Journal Detail:
Title:  Transplantation     Volume:  -     ISSN:  1534-6080     ISO Abbreviation:  Transplantation     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 Department of Pharmacy, University of Washington, Seattle WA. 2 Department of Obstetrics and Gynecology, University of Washington, Seattle WA. 3 Department of Pharmaceutics, University of Washington, Seattle WA. 4 Department of Nursing, University of Washington, Seattle WA. 5 Department of Medicine, University of Washington, Seattle WA. 6 MedStar Health Research Institute, Washington Hospital Center, Georgetown University Medical Center, and Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC. 7 Address correspondence to: Mary F. Hebert, Pharm.D., F.C.C.P., Department of Pharmacy, University of Washington, 1959 NE Pacific Street, H-375 Health Sciences Center, Box 357630, Seattle, WA 98195-7630.
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