Concentrations of cis(Z)-flupentixol in maternal serum,amniotic fluid,umbilical cord serum,and milk

A venous blood sample and an umbilical cord blood sample were obtained from five young women treated with the neuroleptic drug, cis(Z)-flupentixol decanoate in Viscoleo (intramuscularly) or flupentixol (orally) at the time of giving birth. In two cases amniotic fluid was also obtained, and from three of the mothers milk and simultaneous blood samples were obtained in the lactation period. Concentrations of the active drug, cis(Z)-flupentixol were measured in serum, amniotic fluid, and milk by radioimmunoassay. It was found that the concentration of the active drug in umbilical cord serum (fetal serum) was lower than that in serum from the mother — the ratio being about 0.24. Thus the amounts of drug reaching the fetus are low, but they cannot be considered unimportant. The concentrations found in milk were about 30% higher than the serum concentrations. However, the amounts of drug administered to the neonate with the milk are very low and, unless the neonate differs considerably from the adult as to sensitivity to or metabolism of this particular drug, they are of no importance.     

Iodide concentrations in matched maternal serum, cord serum, and amniotic fluid from preterm and term human pregnancies

OBJECTIVES: To characterize the matched maternal and cord plasma and the amniotic fluid concentrations of iodide in preterm and term human pregnancies. METHODS: Specimens were collected at the delivery of 121 singleton pregnancies (92 at term, 29 preterm) with no pre-existing medical complications. Plasma unbound iodide concentrations were measured by the difference between the protein bound iodine and the total iodine measured spectrophotometrically. Total iodide was measured in amniotic fluid. RESULTS: Maternal plasma iodide concentrations were 1.6 +/- 0.4 mcg/dL (mean +/- S.D.) for preterm deliveries and 1.5+/ -0.5 mcg/dL for term deliveries. Cord plasma iodide concentrations were 1.4 +/- 0.5 mcg/dL for preterm deliveries and 1.7 +/- 0.7 mcg/dL for term deliveries. Cord plasma iodide concentrations at birth correlated highly with maternal levels (p < 0.001). The cord:maternal plasma iodide ratio for all pairs was 1.2+/- 0.7. The average cord:maternal plasma iodide ratio was not significantly different between the preterm (0.9+/- 0.4) and term (1.3+/- 0.8) deliveries. Amniotic fluid iodide concentrations did not correlate significantly with cord plasma concentrations. CONCLUSION: Cord plasma concentrations of iodide correlate with paired maternal levels, indicating that, unlike the rabbit and other species, the human conceptus does not highly concentrate iodide.     

Nifedipine concentrations in maternal and umbilical serum, amniotic fluid, breast milk and urine of mothers and offspring.

Eleven hypertensive pregnant patients were treated with nifedipine orally 10 mg thrice daily. At steady state, nifedipine concentration, measured by the high-performance liquid chromatographic method, was 4.3 +/- 1.0 ng/ml (mean +/- s.e.m.) in maternal serum in the third trimester of pregnancy. During delivery, the parent drug levels in maternal and umbilical serum and in amniotic fluid were 12.4 +/- 4.0, 8.6 +/- 2.3 and 2.5 +/- 1.2 ng/ml, respectively. Small amounts of nifedipine were found also in urine of the neonates. In breast milk, the nifedipine concentration was 4.1 +/- 0.8 ng/ml on the third day after delivery. The antihypertensive effect of nifedipine did not correlate with the serum drug concentration. The outcome of pregnancy was favourable in all cases.     

晚期妊娠特发性羊水量异常羊水、母血以及脐血生化分析

目的 探讨晚期妊娠特发性羊水量异常羊水生化成分、孕妇静脉血以及新生儿脐动脉血生化的特点及相关性.方法 对73例晚期妊娠特发性羊水异常患者(59例特发性羊水过少、14特发性羊水过多)进行羊水、孕妇静脉血及新生儿脐动脉血10项生化指标检测和分析,与同期随机选取的40例无妊娠合并症和并发症的单胎足月孕妇进行比较.结果 特发性羊水过少组羊水中钠浓度、钙浓度、葡萄糖及渗透压较正常组降低,肌酐浓度升高,其差异具有显著性(P＜0.0 5);特发性羊水过多组各项羊水生化参数与羊水量正常组未见显著性差异(P＞0.05);各组母血、脐血生化指标未见显著性差异(P＞0.05);特发性羊水过少组钠浓度、氯浓度、钙浓度、肌酐、葡萄糖、渗透压的脐血-羊水梯度较羊水量正常组增高,差异有显著性(P＜0.0 5),羊水多项生化指标与脐血呈正相关.结论 晚期妊娠特发性羊水过少与羊水生化成分的变化密切相关;脐血与羊水的Na 梯度和渗透压梯度可能在羊水量的调节中起作用;母体和胎儿存在维持各自生化内环境稳定的机制;胎儿血生化状态分别与母体生化状态、羊水的生化成分密切相关.     

Comparison of polyfluoroalkyl compound concentrations in maternal serum and amniotic fluid: A pilot study

The extent to which polyfluoroalkyl compounds (PFCs) are detectable in amniotic fluid is unknown. Using paired samples from 28 women, we compared the concentration of 8 PFCs measured in serum, the standard matrix for assessing human exposure, amniotic fluid from routine amniocentesis, and urine. Perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulfonate (PFHxS) were detected in all maternal serum samples. The number of amniotic fluid samples with detectable concentrations differed by PFC (PFOA n=24; PFNA n=10; PFOS n=9; PFHxS n=4). The correlation coefficient between maternal serum and amniotic PFC levels varied considerably by PFC (PFOA ρ=0.64, p<0.001; PFNA ρ=0.05, p=0.9; PFOS ρ=0.76, p=0.01; PFHxS ρ=0.80, p=0.2). Using linear regression, PFOA appeared to be commonly detected in amniotic fluid if the serum concentration exceeded approximately 1.5ng/mL whereas PFOS was rarely detected in amniotic fluid until the serum concentration was about 5.5ng/mL. No PFCs were detected in urine.     

胎儿宫内生长迟缓与母血、脐血、羊水及胎盘中内皮素—1水平关系的研究

目的　探讨胎儿宫内生长迟缓 (intrauterinegrowthretardation ,IUGR)时母血、脐血、羊水及胎盘组织中内皮素 1(ET 1)水平与IUGR发病的关系。方法　 12例IUGR孕妇 ,10例正常孕妇 ,取母血、脐血及胎盘组织 ,用放射免疫法测其ET 1水平。结果　IUGR组胎盘ET 1水平明显高于正常组 ,差异极显著 (P <0 .0 1) ,两组间母血、脐血、羊水中的ET 1水平无差异。两组胎盘ET 1均明显高于母血、脐血、羊水 (P <0 .0 5 ) ,正常组母血、脐血、羊水ET 1水平差异无显著性。结论　胎盘组织中ET 1过高可与IU GR发病有关。     

The clinical usefulness and transference of cefcapene pivoxil (CFPN-PI) into the maternal cubital blood, umbilical blood and amniotic fluid in premature rupture of the membranes

We studied the transference of cefcapene pivoxil (CFPN-PI) into the maternal cubital blood, umbilical blood and amniotic fluid as well as its clinical usefulness. 58 pregnant women without complications who had a premature rupture of membranes after day 0 of the 36th week of pregnancy and delivered a child with a normal transvaginal labor were enrolled this study. As a result, we found that the maternal serum level of CFPN-PI reached a detectable level at 1 hr 15 min post dose, reached the maximum (Cmax) at 2 hr 30 min, and was maintained at 0.15-1.14 micrograms/ml until 4 hr 35 min. In the umbilical serum, the drug concentration reached a detectable level at 1 hr 45 min post dose, was maintained at Cmax of 0.40 microgram/ml from 3 hr 3 min until 4 hr 27 min, and showed a level as high as 0.14 microgram/ml at 7 hr 7 min. In the amniotic fluid, the drug concentration reached a detectable level of 0.09 microgram/ml at 2 hr 48 min post dose, reached Cmax at 3 hr 55 min, and was maintained at 0.15-0.61 microgram/ml until 13 hr 37 min. Concerning the prophylactic effects of CFPN-PI against infections, one case of puerperal intrauterine infection in the parent and two cases of neonatal infection were observed, showing an effectiveness of 95%. In terms of adverse events, neither abnormality in maternal laboratory test data suspected as due to CFPN-PI, nor abnormality in subjective and objective findings was observed. In the neonates, no abnormality suspected as due to CFPN-PI was detected, either, including growth retardation until the 3-month medical examination. We think that CFPN-PI can be a first choice drug for prophylaxis of infections in cases of premature rupture of membranes after the 36th week of pregnancy, because of convenience of oral administration, coupled with excellent safety and potent prophylactic effectiveness against infections resulting from a long term maintenance of high levels in the umbilical blood and amniotic fluid.     

Alpha fetoprotein levels in amniotic fluid and maternal serum and their use in screening in pregnancy.

During the period January 1975--July 1977 alpha fetoprotein was measured in 263 amniotic fluid samples and 44 maternal serum samples taken in the second trimester of pregnancy. The importance of careful interpretation of results is discussed.     

Fundamental and clinical studies on piperacillin in the field of obstetrics and gynecology

Fundamental and clinical studies were made on piperacillin (PIPC) and the results were obtained as follows. Serum and uterine tissue concentrations of PIPC were obtained from 36 to 215 minutes after intravenous single shot of 2 g of PIPC. The cervix uteri, endometrium and corpus uteri showed the highest antibiotic levels of 38.0, 43.0 and 33.0 mcg/g, respectively, at 65 minutes after injection, and oviduct and ovary showed the highest level of 31.5 and 28.5 mcg/g at 36 minutes. Its concentrations were sufficiently effective against the major pathogens (Gram-negative bacilli and anaerobes) demonstrated in the field of obstetrics and gynecology. PIPC was administered 6 patients, including 3 of pelvic peritonitis (isolated organism was E. coli 1), 2 of acute endometritis (Klebsiella sp. 1, Peptococcus sp. + Bacteroides sp. 1) and 1 of acute adnexitis, in a dosage of 1 or 2 g twice or 3 times a day for a period of 5 to 8 days by intravenous administration or intravenous drip infusion. Clinical response was obtained excellent in 1 and good in 5. No adverse reaction as observed in any of the cases treated with PIPC, nor was there any marked changes in the laboratory findings.     

Dichlorodiphenyldichloroethylene concentrations in umbilical cord of newborns and determinant maternal factors

OBJECTIVE: The aim was to identify exposure levels to dichlorodiphenyltrichloroethane (DDT) and to assess maternal factors as determinants of the serum dichlorodiphenyldichloroethylene (DDE) concentration in umbilical cord in newborns from the Mexican Pacific coastal area of Oaxaca State. MATERIALS AND METHODS: A cross-sectional study was conducted of 86 paired mothers and newborns from the Oaxaca community of Pochutla. Blood and umbilical cord blood samples were collected to determine DDT and DDE by GC. Information concerning possible determinant factors with regard to pesticide concentration was obtained by means of a questionnaire. RESULTS: A positive correlation between maternal and umbilical cord serum DDE concentration was observed (geometric mean of 7.69 microg g(-1) and 7.29, respectively). Multiple analyses showed that significant maternal factors related to umbilical cord serum DDE concentrations were: always having lived in the same community; low to high socioeconomic strata; accumulated breast-feeding time. CONCLUSIONS: The determinant factors observed in this study must be considered in future studies for the quantification of organochlorine concentration. In addition, these factors must be taken into account when preventive actions to minimize in utero exposure to these pesticides are carried out.     

产妇血清和新生儿脐带血中总 IgE 与特应性皮炎的关系及过敏原检测

摘要： 目的 探讨产妇血清和新生儿脐带血中总IgE与儿童特应性皮炎（AD）的相关性及过敏原检测的临床意义。方法 选取2009-2011年建立的出生队列中诊断为AD的儿童35例（AD组）,随机选取未患AD的35例儿童作为对照（对照组）,ELISA法分别检测儿童出生前产妇血清和新生儿脐带血中的总IgE水平,定量免疫印迹法检测血清特异性IgE水平。 结果 AD组中母亲血清和新生儿脐带血总IgE阳性率高于对照组(χ2分别为16.568和14.933,均P < 0.01)。AD组中母亲血清过敏原中尘螨,屋尘,豚草花粉,嵩类花粉,杨、柳及榆树花粉,霉菌,虾,海洋鱼类特异性IgE阳性率高于对照组（均P < 0.05）;AD患儿脐带血过敏原中嵩类花粉,霉菌IgE阳性率高于对照（均P < 0.05）。结论 母亲血清总IgE升高可能会对婴儿后期罹患AD起预测作用;母亲的过敏状态与婴儿的过敏状态无明显一致性。     

Differential protein binding of indinavir and saquinavir in matched maternal and umbilical cord plasma

AIMS: To determine whether lower umbilical cord than maternal binding of indinavir and saquinavir contributed to the low cord : maternal (C : M) total concentration ratios reported previously. METHODS: Indinavir and saquinavir unbound fraction (fu) was determined using equilibrium dialysis. Buffer solutions of human serum albumin (HSA) (20.0, 30.0, 40.0 g l(-1)) and alpha(1)-acid glycoprotein (AAG) (0.20, 0.60, 2.00 g l(-1)) were spiked with indinavir (1.00 and 8.00 mg l(-1)) or saquinavir (0.15 and 1.50 mg l(-1)). Matched maternal and umbilical cord plasma was spiked with 1.00 mg l(-1) indinavir (n = 12) or 0.15 mg l(-1) saquinavir (n = 20). Spiked protein/plasma solutions were dialyzed against isotonic phosphate buffer, at 37 degrees C. At equilibrium, indinavir and saquinavir concentrations were quantified, and the f(u) determined. RESULTS: Indinavir and saquinavir demonstrated protein concentration-dependent binding in buffer solutions of HSA and AAG. Indinavir f(u) was significantly higher in umbilical cord (0.53 +/- 0.12) compared with maternal (0.36 +/- 0.11) plasma (95% CI of the difference -0.26, -0.097). Similarly, saquinavir fu was different between umbilical cord (0.0090 +/- 0.0046) and maternal plasma (0.0066 +/- 0.0039) (95% CI of the difference -0.0032, -0.0016). The transplacental AAG concentration gradient contributed significantly to the binding differential of both drugs. CONCLUSIONS: The differential plasma binding of both drugs, which was largely the result of the transplacental AAG concentration gradient, would contribute to the low C : M total plasma concentration ratios observed previously. Unbound concentrations of indinavir and saquinavir are likely to be substantially lower in umbilical cord than maternal plasma.     

Fundamental study of piperacillin sodium in term and premature neonates

Piperacillin sodium (PIPC) is a semisynthetic penicillin displaying high antibacterial activities against Gram-positive and Gram-negative bacteria including Pseudomonas sp., Proteus sp., etc. It acts bactericidally and is stable against beta-lactamases. The usefulness of PIPC in the treatment of infections in mature and premature neonates was investigated and the following results were obtained. The pharmacokinetics (half-life, distribution volume, total body clearance) of PIPC after 50 mg/kg intravenous drip infusion in 10 cases of neonates were examined. Relationship between T1/2 and hours after birth was clearly determined. Adverse effects and abnormality in laboratory test values were not observed. It is considered from the above results that PIPC may be an useful antibacterial agent for the treatment of infections in neonates.     

高效液相色谱-紫外检测法测定母体静脉及新生儿脐动、静脉血内瑞芬太尼血药浓度

目的建立高效液相色谱紫外检测法测定人血中瑞芬太尼(镇痛药)血药浓度。方法用1-氯丁烷提取全血中的瑞芬太尼,选用GI97559(瑞芬太尼乙基类似物)为内标定量。色谱柱为ZobarSE-CN(4.6mm×250mm,5μm),流动相为乙腈-甲醇-磷酸二氢钾缓冲液,柱温30℃,流量1.5mL·min-1,紫外检测波长210nm,按内标法定量。结果标准曲线在1～20ng·mL-1范围内,浓度与峰面积比有良好的线性关系(γ=0.956)。结论本方法操作简便、试剂成本低、灵敏度高、精密度好,为临床研究瑞芬太尼血药浓度提供一种较好的分析技术。     

Pharmacokinetic studies on the concomitant administration of piperacillin and cefazolin, and piperacillin and cefoperazone in rabbits

The pharmacokinetics of each drug on the concomitant administration of piperacillin (PIPC) and cefazolin (CEZ) or cefoperazone (CPZ) were studied in rabbits. When rabbits received the consecutive drip infusion administration of CEZ (0.71 mg/kg/minute) and PIPC (1.38 mg/kg/minute) and likewise of CPZ (0.72 mg/kg/minute) and PIPC (1.54 mg/kg/minute) for 1 hour, respectively, the serum half-lives of CEZ and CPZ were respectively prolonged about 1.8 and 1.6 times during drip infusion of PIPC than administered alone. However, when the sequence of administration were reversed, the serum levels of PIPC were not affected by the consecutive drip infusion administration of CEZ and CPZ. To study these findings in detail, the single intravenous dose of 20 mg/kg of CEZ and CPZ were administered under drip infusion of PIPC (2.65-2.93 mg/kg/minute). The serum half-lives of CEZ and CPZ were also prolonged about 5.4 and 1.9 times, respectively, whereas urinary excretion of CEZ, and urinary and biliary excretion of CPZ were reduced by PIPC. Moreover, when the single intravenous dose of 20 mg/kg of PIPC were administered under drip infusion administration of CEZ (0.96-2.60 2.60 mg/kg/minute), the pharmacokinetics of PIPC was not affected by the presence of CEZ. However, under drip infusion administration of CPZ (2.60-2.70 mg/kg/minute), the PIPC serum half-life was prolonged about 1.4 times, and biliary excretion of PIPC was reduced but urinary excretion was not. From the results of renal clearance experiments, tubular secretion appeared to be the predominant mechanism of renal elimination for these three drugs. These results indicate that PIPC influences the pharmacokinetics of both drugs by the competitively inhibiting tubular secretion in CEZ, and tubular secretion and hepatic transport system in CPZ. Therefore, in this respect PIPC seems to have probenecid-like action.