Citalopram serum and milk levels in mother and infant during lactation

We present a case of intensified therapeutic drug monitoring (TDM) of citalopram in mother and newborn infant after clinically observed selective serotonin reuptake inhibitor (SSRI)-associated symptoms 2 weeks until 2 months after delivery. The SSRI-associated symptoms observed in the infant (up to 3 weeks after delivery) were irregular breathing, sleep disorders, hypotonia, and hypertonia. We conclude that the SSRI-associated symptoms in the infant represent citalopram withdrawal effects rather than side effects caused by breastfeeding. This case illustrates the importance of a flexible TDM program and a multidisciplinary approach in a hospital setting to deal with cases of drug-associated adverse effects, such as SSRI withdrawal effects.     

Ethosuximide in epileptic women during pregnancy and lactation period. Placental transfer, serum concentrations in nursed infants and clinical status

A total of 10 epileptic mothers treated with ethosuximide (ES) as well as their 13 newborns were included in this study. At birth foetal/maternal serum concentration ratios were 0.97 +/- 0.02 (n = 7) and ES half-lives in three neonates were 32, 37 and 38 h. The breast milk concentrations of ES were similar to those in maternal serum (milk/serum: 0.86 +/- 0.08, n = 12) and the nursed infants maintained serum levels between 15 and 40 micrograms/ml. Two major malformations (bilateral clefting, hare-lip) were observed in two neonates whose mothers received either ES/PB or ES/PMD comedication. The number of minor anomalies was higher in the ES group (6.2, n = 12) than in the pair-matched control group of infants born to non-epileptic mothers (2.1, n = 10). Neonatal behaviour complications occurred in seven infants, two of them were severely affected.     

Nitrendipine in human plasma and breast milk

Summary To assess the disposition of the dihydropyridine calcium antagonist, nitrendipine, in lactating mothers, we studied three breast-feeding women to determine simultaneous plasma and breast milk concentrations of nitrendipine and its inactive pyridine analog metabolite after both a single 10 mg oral dose and 5 days of continuous therapy (20 mg per day).Nitrendipine was excreted in breast milk at peak concentrations ranging from 4.3 to 6.5 ng/ml 1–2 h after acute dosing while its inactive pyridine metabolite ranged from 6.9 to 11.9 ng·ml^–1. After 5 days of dosing, C_max remained in the same range and the breast milk/whole plasma concentration ratio for nitrendipine was 0.2 to 0.5. On the fourth day of continuous dosing, average concentrations of nitrendipine from 24-h collections of the milk were 1.1 to 3.8 ng·ml^–1.Thus, nitrendipine and its metabolite are excreted in very low concentrations in human breast milk. Based on a maternal dose of 20 mg daily, a newborn infant would ingest an average of 1.7 µg of nitrendipine per day, or a relative dose of 0.095%.Presented in part at the 3rd Annual Meeting of the American Society of Hypertension, New York, N.Y., June 24, 1988     

Concentrations of lamotrigine in a mother on lamotrigine treatment and her newborn child

Objective: To investigate the transfer of lamotrigine in pregnancy and during lactation from a mother on lamotrigine treatment to her child. Methods: Concentrations of lamotrigine were measured by high-pressure liquid chromatography in umbilical cord serum and in serum samples of the mother and her child as well as in the mother's milk during the first five postpartum months. Results: In the child lamotrigine serum concentrations (up to 2.8 μg ml⁻¹) comparable to those usually achieved in active treatment with lamotrigine were found not only after birth, but also during lactation. A considerable amount of lamotrigine (2–5 mg per day) was excreted in breast milk. No adverse effects were seen in the child. Conclusion: The transfer of lamotrigine taking place during pregnancy and lactation should not be neglected. In this case the child should be thoroughly observed for potential adverse effects. Received: 27 June 1996 / Accepted: 7 October 1996     

服用阿莫西林母亲哺乳的婴儿出现血小板减少性紫癜

1例56 d男婴因血小板减少性紫癜入院。入院前2 d其母行输卵管结扎手术,术后口服阿莫西林预防感染,服药期间未停止哺乳。服药第2天晚患儿下肢皮肤出现散在针尖大小红点,第3天左下肢出现瘀斑。入院时血小板4×109/L,经骨髓细胞学检查,确诊为血小板减少性紫癜。停止哺乳,予以支持治疗,2周后患儿治愈出院。     

Olanzapine excretion in human breast milk: estimation of infant exposure

Newer antipsychotic drugs offer significant clinical advantages for the treatment of psychosis. In particular for the treatment of postpartum disorders newer agents may be suited due to their favourable side-effect profiles. Of concern is the passage of the drugs into breast milk and what potential risks this poses for an infant who is breastfed. The excretion of olanzapine into the breast milk of five lactating women with postpartum psychosis was examined in this study. Nine pairs of plasma and breast-milk samples were collected and the concentration of olanzapine determined by high-performance liquid chromatography. Single-point milk-to-plasma ratios were calculated and ranged from 0.2 to 0.84 with a mean of 0.46. The median relative infant dose was 1.6% (range 0-2.5%) of the weight-adjusted maternal dose. During the study period, there were no apparent ill effects on the infant as a consequence of exposure to these doses of olanzapine. As with other antipsychotic drugs this study demonstrates that olanzapine passes into breast milk. The long-term effects of exposure in infants exposed to olanzapine requires further investigation.     

Distribution of indomethacin in human milk and estimation of its milk to plasma ratio in vitro

1. The distribution of indomethacin in fat and protein fractions of colostrum and mature milk as well as its milk to plasma drug concentration ratio (M/P ratio) were determined in vitro. 2. The extent of plasma protein binding of indomethacin (5-20 microg ml(-1)) was > or = 99.6%. The protein binding of indomethacin in colostrum was 46.0% at pH 7.4. The lower protein content of mature milk compared with colostrum was associated with a significant decrease in the extent of drug protein binding (46 +/- 1.93 to 35 +/- 1.0 s.e. mean). Protein binding was also decreased significantly in 8% fat mature milk (20.3 +/- 2.4 s.e mean) but was constant over the pH range 7.4 to 6.8. 3. About 40% of indomethacin added to milk was associated with the fatty layer. The indomethacin M/P ratio determined by equilibrium dialysis was less than 0.01. Hence the maximum infant daily dose was estimated to be 0.006 mg kg(-1). 4. Our results indicate that indomethacin transfers to milk by simple diffusion according to its physicochemical properties, and that treatment with indomethacin is not a contraindication to breast feeding.     

母婴同室前后剖宫产分析

目的　探讨母婴同室及母乳喂养对于割宫产产妇子宫复旧及乳汁分泌的影响。方法　随机抽取我院产科1999年8月割宫产病例100例，均为母婴同室及母乳喂养，与1993年同期非母婴同室及母乳喂养的割宫产病例100例进行对比分析。结果　母婴同室及母乳喂养较非母婴同室及母乳喂养的剖宫产产妇子宫复旧更好，乳汁分泌早且量较多，初乳利用冯高。结论　剖宫产产妇实行母婴同室及按需哺乳，既有利于产妇的产后恢复，又能促进乳汁分泌，使婴儿得到营养丰富、含有多种抗体的初乳。     

Sensitivity of the young infant to drug exposure through human milk

In spite of significant exposure to drugs and chemicals through breast milk, there are very few reports of documented adverse effects on the infant. It is perhaps appropriate to consider that the presence of drugs and chemicals in milk may have a positive effect on developmental processes of the young infant. New experimental techniques coupled with increasing sensitive assays for chemical moieties present opportunities for measuring the effect of such chemicals on development processes in the neonate and young infant.     

Prediction of drug concentrations in human skim milk from plasma protein binding and acid-base characteristics.

1. Protein binding in human skim milk of a series of seven drugs with diverse plasma protein binding and acid-base characteristics, was measured by ultrafiltration. 2. A mathematical relationship between plasma and skim milk unbound fractions was established using measured values from this study along with values from the literature. 3. The relationship enables prediction of unknown protein binding values of drugs in skim milk from known plasma protein binding values. 4. Knowledge of milk protein binding enables a more accurate assessment of total milk concentrations than is available from existing theory which is limited to prediction of unbound drug.     

无痛分娩对母婴影响的临床分析

目的观察和分析无痛分娩对母婴的影响。方法选取在我院分娩的产妇180例的临床资料,其中,无痛分娩组90例,常规分娩组90例产妇。观察两组产妇分娩过程中相关指标变化情况。结果无痛分娩组产妇的疼痛评分为（3.1±1.2）分,明显低于常规分娩组（P〈0.05）;且无痛分娩组11例产妇改剖宫产,而常规分娩组39例产妇改剖宫产（P〈0.05）。两组产妇其他指标,如第二产程时间、使用催产素例数、新生儿1min阿普加评分以及产后出血量等基本相当（P〉0.05）。结论无痛分娩在各项临床指标上,同常规分娩效果相当,并在一定程度上优于常规分娩（降低剖宫产率等）,值得向临床推荐。     

Benefits and risks to mother and infant of drug treatment for postnatal depression.

The postnatal period presents a special problem to healthcare providers treating psychiatric disorders in women. Many new mothers who need antidepressant treatment may wish to breastfeed their infants, but are hesitant to do so for fear of passing on possible harmful effects of the medication through their milk. The focus of this article will be on highlighting and interpreting the existing literature on the benefits and risks to mother and infant of drug treatment for postnatal depression, as well as outlining treatment guidelines for the use of antidepressants in breastfeeding mothers. The article will specifically focus on the use of fluoxetine, sertraline, paroxetine, fluvoxamine and citalopram, which are more commonly used and belong to the selective serotonin reuptake inhibitor group of antidepressants. The tricyclic and other newer antidepressant medications will also be discussed. As there are no published controlled studies on the use of antidepressants by breastfeeding women, publications of individual case reports, case series, and pharmacokinetic investigations serve as the basis for the development of treatment guidelines. Results from this growing body of literature are promising in that, with the exception of a few cases, no serious adverse events have been reported in infants exposed to antidepressant medications through breast milk. In addition nonpharmacological treatments consisting of different types of psychotherapies will be discussed. It is critical that healthcare providers evaluate each mother-infant dyad on an individual basis when faced with the decision to prescribe antidepressant medications during the postnatal period.     

Transfer of aciclovir from plasma to human breast milk

Aciclovir (CAS 59277-89-3) is frequently used in herpes simplex virus diseases, but administration to lactating women occurs only rarely. Therefore, information about the pharmacokinetics of aciclovir in human breast milk is limited. The concentration in breast milk is 2 to 3 fold increased compared to plasma. The reason for this increase is unknown until now. An active transport mechanism has been assumed. The aim of this study was to prove whether the higher concentration of aciclovir in human breast milk is due to only a passive transfer. Two chambers separated by a semipermeable membrane were used. The first chamber contained plasma with aciclovir, the second chamber breast milk without aciclovir. The increase in aciclovir concentration in the second chamber was determined. The concentration of aciclovir in breast milk exceeded that of plasma after 2 h and reached a higher concentration. Thus, the higher aciclovir concentration in human breast milk is due to passive diffusion. No active transport mechanism is needed.