Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava, Syllabova 19, 703 00 Ostrava, Czech Republic; Department of Clinical Pharmacology, Department of Laboratory Medicine, University Hospital Ostrava, 17. listopadu 1790, 700 30 Ostrava, Czech Republic.
Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava, Syllabova 19, 703 00 Ostrava, Czech Republic.
Biomed Pharmacother. 2021 May;137:111412. doi: 10.1016/j.biopha.2021.111412. Epub 2021 Feb 24.
To receive information about carbamazepine and its active metabolite 10,11-epoxide transport into mature milk and suckling infants.
In this cohort study, maternal serum, mature milk, and infant serum carbamazepine and epoxide levels were measured between the 6th and 29th postnatal day (carbamazepine in 1990-2017, epoxide in 1997-2017). Paired maternal serum, infant serum and milk levels were used for the assessment of ratios of this levels. The influence of combined treatment with enzyme-inducing antiepileptic drugs and valproic acid was assessed. Relationship between maternal serum, infant serum, and milk levels was also evaluated.
Maternal carbamazepine levels were 1.4-10.4 mg/L, milk 0.5-6.7 mg/L and infant 0.5-2.6 mg/L. Maternal 10,11-epoxide levels were 0.3-5.4 mg/L, milk 0.3-3.7 mg/L and infant 0.3-0.6 mg/L. Highly significant correlations were observed exclusively between milk and maternal serum levels of both carbamazepine and 10,11-epoxide. Concomitant administration of enzyme-inducing antiepileptic drugs significantly increased the maternal apparent oral clearance of carbamazepine by approximately 130%. Carbamazepine combined with valproic acid significantly increased epoxide levels in milk and maternal serum but not in breastfed infants.
In breastfed infants, carbamazepine levels did not reach the lower limit of the therapeutic range used for the general epileptic population, and the majority of epoxide levels were less than the lower limit of quantification. Routine monitoring of carbamazepine in these infants is not compulsory. However, observation of breastfed infants is desirable. If signs of potential adverse reactions are evident, infant serum concentrations should be monitor.
了解卡马西平及其活性代谢物 10,11-环氧的转运进入成熟乳和哺乳婴儿的情况。
在这项队列研究中，于产后第 6 至 29 天测量了母体血清、成熟乳和婴儿血清中的卡马西平及其环氧水平（1990-2017 年测量卡马西平，1997-2017 年测量环氧）。使用配对的母体血清、婴儿血清和乳汁水平来评估这些水平的比值。还评估了联合使用酶诱导抗癫痫药物和丙戊酸治疗的影响。同时还评估了母体血清、婴儿血清和乳汁水平之间的关系。
母体卡马西平水平为 1.4-10.4mg/L，乳汁 0.5-6.7mg/L，婴儿 0.5-2.6mg/L。母体 10,11-环氧水平为 0.3-5.4mg/L，乳汁 0.3-3.7mg/L，婴儿 0.3-0.6mg/L。仅在卡马西平和 10,11-环氧的乳汁和母体血清水平之间观察到高度显著的相关性。同时使用酶诱导抗癫痫药物会使母体卡马西平的表观口服清除率增加约 130%。卡马西平与丙戊酸联合使用会显著增加乳汁和母体血清中的环氧水平，但不会增加母乳喂养婴儿中的环氧水平。
在母乳喂养的婴儿中，卡马西平水平未达到一般癫痫人群使用的治疗范围下限，且大多数环氧水平低于定量下限。因此，这些婴儿不需要常规监测卡马西平。但是，有必要观察母乳喂养的婴儿。如果出现潜在不良反应的迹象，应监测婴儿血清浓度。
