title: Interpreting tacrolimus concentrations during pregnancy and postpartum.
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.
authors.affiliation: Department of Pharmacy, University of Washington, Seattle, WA 98195-7630, USA.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Hebert
authors.forename: Songmao
authors.initials: S
authors.lastname: Zheng
authors.forename: Karen
authors.initials: K
authors.lastname: Hays
authors.forename: Danny D
authors.initials: DD
authors.lastname: Shen
authors.forename: Connie L
authors.initials: CL
authors.lastname: Davis
authors.forename: Jason G
authors.initials: JG
authors.lastname: Umans
authors.forename: Menachem
authors.initials: M
authors.lastname: Miodovnik
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Thummel
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Easterling
mesh_terms: D001942:Breast Feeding; D016903:Drug Monitoring; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005333:Fetus / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D008895:Milk, Human / Q000378:metabolism; D016377:Organ Transplantation; D021041:Placental Circulation; D049590:Postpartum Period / Q000097:blood*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D011485:Protein Binding; D018570:Risk Assessment; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus