Interpreting tacrolimus concentrations during pregnancy and postpartum. [Review]

MedStar author(s):
Citation: Transplantation. 95(7):908-15, 2013 Apr 15.PMID: 23274970Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., Extramural | ReviewSubject headings: *Drug Monitoring | *Immunosuppressive Agents/bl [Blood] | *Organ Transplantation | *Postpartum Period/bl [Blood] | *Pregnancy Complications/pc [Prevention & Control] | *Tacrolimus/bl [Blood] | Breast Feeding | Female | Fetal Blood/me [Metabolism] | Fetus/de [Drug Effects] | Humans | Immunosuppressive Agents/ae [Adverse Effects] | Immunosuppressive Agents/pk [Pharmacokinetics] | Maternal Exposure | Maternal-Fetal Exchange | Milk, Human/me [Metabolism] | Placental Circulation | Pregnancy Complications/bl [Blood] | Pregnancy Complications/im [Immunology] | Pregnancy | Protein Binding | Risk Assessment | Risk Factors | Tacrolimus/ae [Adverse Effects] | Tacrolimus/pk [Pharmacokinetics]Year: 2013Local holdings: Available online from MWHC library: 1996 - present, Available in print through MWHC library: 1999 - 2006ISSN:
  • 0041-1337
Name of journal: TransplantationAbstract: 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.All authors: Davis CL, Easterling TR, Hays K, Hebert MF, Miodovnik M, Shen DD, Thummel KE, Umans JG, Zheng SFiscal year: Digital Object Identifier: Date added to catalog: 2013-09-17
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article Available 23274970

Available online from MWHC library: 1996 - present, Available in print through MWHC library: 1999 - 2006

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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