Tacrolimus placental transfer at delivery and neonatal exposure through breast milk

被引:64
作者
Zheng, Songmao [1 ]
Easterling, Thomas R. [2 ,3 ]
Hays, Karen [4 ]
Umans, Jason G. [6 ,7 ,8 ]
Miodovnik, Menachem [6 ,7 ]
Clark, Shannon [9 ]
Calamia, Justina C. [1 ]
Thummel, Kenneth E. [1 ]
Shen, Danny D. [1 ,3 ]
Davis, Connie L. [5 ]
Hebert, Mary F. [2 ,3 ]
机构
[1] Univ Washington, Dept Pharm, Seattle, WA 98195 USA
[2] Univ Washington, Dept Obstetr & Gynecol, Seattle, WA 98195 USA
[3] Univ Washington, Dept Pharm, Seattle, WA 98195 USA
[4] Univ Washington, Dept Nursing, Seattle, WA 98195 USA
[5] Univ Washington, Dept Med, Seattle, WA 98195 USA
[6] MedStar Hlth Res Inst, Washington, DC USA
[7] MedStarWashington Hosp Ctr, Washington, DC USA
[8] Georgetown Howard Univ Ctr Clin & Translat Res, Washington, DC USA
[9] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA
关键词
breast milk; neonatal exposure; placental transfer; pregnancy; tacrolimus; unbound drug concentration; LIVER-TRANSPLANT RECIPIENTS; PLASMA-PROTEIN BINDING; P-GLYCOPROTEIN; ORAL BIOAVAILABILITY; CYCLOSPORINE-A; WHOLE-BLOOD; IN-VITRO; PREGNANCY; PHARMACOKINETICS; DRUGS;
D O I
10.1111/bcp.12122
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
AIM(S) The current investigation aims to provide new insights into fetal exposure to tacrolimus in utero by evaluating maternal and umbilical cord blood (venous and arterial), plasma and unbound concentrations at delivery. This study also presents a case report of tacrolimus excretion via breast milk. METHODS Maternal and umbilical cord (venous and arterial) samples were obtained at delivery from eight solid organ allograft recipients to measure tacrolimus and metabolite bound and unbound concentrations in blood and plasma. Tacrolimus pharmacokinetics in breast milk were assessed in one subject. RESULTS Mean (+/-SD) tacrolimus concentrations at the time of delivery in umbilical cord venous blood (6.6 +/- 1.8 ng ml(-1)) were 71 +/- 18% (range 45-99%) of maternal concentrations (9.0 +/- 3.4 ng ml(-1)). The mean umbilical cord venous plasma (0.09 +/- 0.04 ng ml(-1)) and unbound drug concentrations (0.003 +/- 0.001 ng ml(-1)) were approximately one fifth of the respective maternal concentrations. Arterial umbilical cord blood concentrations of tacrolimus were 100 +/- 12% of umbilical venous concentrations. In addition, infant exposure to tacrolimus through the breast milk was less than 0.3% of the mother's weight-adjusted dose. CONCLUSIONS Differences between maternal and umbilical cord tacrolimus concentrations may be explained in part by placental P-gp function, greater red blood cell partitioning and higher haematocrit levels in venous cord blood. The neonatal drug exposure to tacrolimus via breast milk is very low and likely does not represent a health risk to the breastfeeding infant.
引用
收藏
页码:988 / 996
页数:9
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