Transplacental passage of atenolol in man

Summary Maternal and umbilical serum concentrations of atenolol, a hydrophilic, cardioselective beta-adrenoceptor antagonist, were studied at delivery in seven cases of pregnancy hypertension. The drug had been administered to each patient for at least one week. Atenolol was detected in both maternal and umbilical serum in six cases, showing that there is transplacental passage of the drug. In the seventh case, who had stopped taking atenolol more than one day before delivery, neither maternal nor umbilical serum contained a measurable quantity of the drug. Atenolol concentration varied 3- to 6-fold between individuals, but there was no systematic difference between maternal and umbilical levels. It seems reasonable to assume that during steady state conditions the blood level of atenolol in mother and fetus is approximately equal, and that fetal accumulation of the drug does not occur.     

The effect of hydralazine on steady-state plasma concentrations of metoprolol in pregnant hypertensive women

Summary We have studied the plasma concentrations levels of metoprolol after its twice daily administration in a dose of 50 mg for 4 days in ten, hypertensive pregnant women to the during monotherapy and in combination with 25 mg of hydralazine given twice daily.Hydralazine increased the median AUC and C_max of metoprolol by 38% and 88% respectively, and decreased the t_max from 1.5 h to 1.0 h.Hydralazine had no effect on the plasma concentrations of alpha-OH-metoprolol.These results suggest that the effect of hydralazine on metoprolol plasma concentrations is primarily due to a reduction in first-pass elimination.     

Transfer of labetalol into amniotic fluid and breast milk in lactating women

Summary The transfer of labetalol into human breast milk and amniotic fluid was studied in women with pregnancy hypertension. The women were treated with labetalol 600–1200 mg daily. The ratio between the areas under the milk and plasma concentration versus time curves varied between 0.8 and 2.6. No consistent relation between milk and plasma concentration in the mother was observed either within the individuals during a dose interval or between different individuals. One of the nursed infants at the end of the dose interval had a plasma labetalol in the same range as the mother, and in another infant the level was below the detection limit. Amniotic fluid concentrations 2–3 h after dosing were generally lower than in plasma.     

Hydroxychloroquine in human breast milk

Summary Hydroxychloroquine 3.2 µg was detected in breast milk from a woman given 800 mg over 48 hour.     

Piroxicam in human breast milk

Summary In 2 nursing women, piroxicam was present in breast milk at about 1% of the concentration in maternal serum. None was detected in serum from the baby fed by one of them.     

Tacrolimus placental transfer at delivery and neonatal exposure through breast milk

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.     

Comparison of labetalol,propranolol and hydralazine in hypertensive out-patients

Summary In a randomised cross-over trial the combination labetalol/hydrochlorothiazide was compared with the combination of propranolol/hydralazine/hydrochlorothiazide in 34 uncomplicated hypertensive patients, who were not satisfactorily controlled with hydrochlorothiazide 50 mg alone. The elevated diastolic pressure (D.P.) in 27 patients responded satisfactorily to the labetalol schedule and in 28 patients to the propranolol/hydralazine schedule. No difference was found in the rate of decrease of D.P., nor in the disappearance of hypertension — related complaints. Although the duration of the washout between treatments was at least one month, treatment was significantly more efficacious during the second period. Labetalol pre-treatment especially seemed to enhance the effect of subsequent propranolol/hydralazine administration. Side effects due to therapy were rare and were not related to any particular treatment. The median daily dose of labetalol in responders was 600 mg and that of propranolol/hydralazine 120/60 mg (in both therapies hydrochlorothiazide 50 mg was given in addition). Patients showed a slight preference for the labetaol medication. It is concluded that labetalol/hydrochlorothiazide and propranolol/hydralazine/hydrochlorothiazide are equally satisfactory in the treatment of uncomplicated hypertension.     

Excretion of oxazepam in breast milk

Summary Oxazepam was measured in plasma and breast milk during 3 days of medication and 10 and 34 h after the last dose. The half-life estimated from levels in plasma and milk was approximately 12 hours. Less than 1/1000 of the maternal dose would have been excreted in 11 breast milk.     

Excretion of gold into human breast milk

Summary After the administration of 70 mg and 50 mg aurothiomalate, respectively, to 2 patients with rheumatoid arthritis, significant amounts of gold appeared in breast milk.     

Excretion of paracetamol in human breast milk

Summary Breast milk and plasma levels of paracetamol were monitored in 3 lactating women after ingestion of a single 500 mg dose of paracetamol. The paracetamol concentrations were consistently lower in milk, with a mean milk/plasma AUC ratio of 0.76. This value was in close agreement with the milk/plasma partition ratio of 0.81 foundin vitro, and could be related to quantitative binding differences between the two fluids. The half-lives of paracetamol in plasma and breast milk were almost identical, with an overall mean of 2.7 h. As less than 0.1% of the maternal dose would be present in 100 ml milk, breast feeding need not be discontinued due to paracetamol treatment in conventional dosage.     

Verapamil and norverapamil in plasma and breast milk during breast feeding

Summary The concentrations of verapamil and norverapamil have been measured in milk and plasma samples from a 32year-old woman treated with verapamil 80 mg tds while breast-feeding her child.The average steady-state concentrations of verapamil and norverapamil in milk were, respectively, 60% and 16% of the concentrations in plasma.The breast-fed child received less than 0.01% of the dose of verapamil given to the mother. No verapamil or norverapamil (<1 ng/ml) could be detected in the plasma from the child.     

高效液相色谱法测定乳汁和血浆中的氟比洛芬浓度

目的：建立高效液相色谱法检测产妇母乳和血浆中氟比洛芬的方法,用于评估产妇乳汁/血药浓度百分比。方法：以卡马西平为内标,乳汁和血浆样品加入1 mol·L^-1的盐酸溶液后用正己烷：乙酸乙酯（1：4）萃取,选择C₁₈柱检测,以甲醇-6.85 mmol·L^-1磷酸-乙腈（30：40：30）为流动相,流速为1.0 mL·min^-1,检测波长为247 nm,柱温为30℃。结果：乳汁和血浆中氟比洛芬的浓度分别在0.02~5.00 μg·mL^-1（R²=0.999 7）和0.05~10.00 μg·mL^-1（R²=0.999 2）内线性关系良好,日内、日间RSD均低于6%。20例产妇24,36,48 h的乳汁/血药浓度百分比分别为6.87%,6.33%,6.58%。结论：该方法快速、简便、灵敏度高、重现性好。氟比洛芬在乳汁中分布较少。     

Presence of chlorprothixene and its metabolites in breast milk

Summary Chlorprothixene (CPX) and CPX sulphoxide were demonstrated in breast milk from two psychotic mothers taking 200 mg CPX daily. The milk concentrations of CPX were 120 to 260% greater than in plasma. The estimated amounts of drug administered in breast milk to one of the infants were 15 and 26 µg/day for CPX and CPX sulphoxide, respectively. Accordingly, the infant dose of the parent compound would be only 0.1% of the maternal dose/kg body weight. It is not likely that CPX or its metabolite would exert any immediate pharmacological effects in the nursing infant. However, the long term effect of low doses of neuroleptic drugs in the developing infants is not yet known.     

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     

高效液相色谱法测定母乳中的奥硝唑浓度

目的:建立测定母乳中奥硝唑浓度的反相高效液相色谱法.方法:色谱柱为C18柱(4.0 mm×150 mm,4 μm),流动相为甲醇-水(30∶70),流速0.8mL·mim-1,检测波长318 nm,柱温25℃.母乳样品经氯仿-异丙醇(95∶5)提取,挥干,用流动相溶解,进行色谱分析.结果:母乳中内源性物质不干扰奥硝唑的测定,奥硝唑在1.96～29.40 mg·L-1浓度范围内峰面积与浓度呈良好的线性关系,r=0.9994,最低检测限为0.16 mg·L-1.平均回收率为(99.7±0.6)%,高、中、低3个浓度的日内RSD≤4.8%,日间RSD≤4.9%.结论:方法灵敏、准确,重现性好,可用于奥硝唑在母乳中的药动学研究.     

Plasma and human milk concentrations of moclobemide in nursing mothers

Plasma and breast milk concentrations of the monoamine oxidase-A inhibitor, moclobemide were measured in eight women being treated for post-partum depression. The main milk to plasma ratio was 0·68, with a range of 0·39–1·21. There was no correlation between this ratio and dose of the drug. Based on the milk to plasma ratio, the infants were exposed to <1% of the maternal dose. This exposure did not appear to have any adverse effects on the infants' developmental milestones as judged by clinical observation. Long term follow up of these children and further study of within day variations in plasma and breast milk moclobemide after chronic dosage are required. Copyright © 1998 John Wiley & Sons, Ltd.     

The effects of nifedipine and hydralazine induced hypotension on sympathetic activity

Summary To determine whether inhibition of sympathetic activity is a factor in calcium antagonist induced hypotension, plasma noradrenaline was measured after intravenous infusion of hydralazine (25 mg) and the calcium antagonist nifedipine (4 mg) in 6 hypertensive males. The resultant reduction in mean blood pressure (12.4% and 14.2% respectively) was accompanied by similar increases in heart rate and plasma noradrenaline concentration. These results suggest that calcium slow channel blockade does not inhibit noradrenaline release from sympathetic nerves and that nifedipine induced hypotension is independent of such a mechanism.     

Excretion of citalopram in breast milk

Aims The objective of this study was to measure the secretion of the selective serotonin uptake inhibitor citalopram in breast milk.
Methods The excretion of citalopram in breast milk was studied at steady-state conditions in two patients with depression and in one healthy volunteer after ingestion of a single dose citalopram.
Results Milk/serum concentration ratios based on single pairs of samples from the two patients ranged from 1.16 to 1.88. Based on milk concentration data from the patients, the absolute dose ingested by a suckling infant would be 4.3–17.6  μg  kg⁻¹ day⁻¹, and the relative dose 0.7–5.9% of the weight-adjusted maternal dose. Based on area-under-the-time-concentration curves from the healthy volunteer, the milk/serum ratio was 1.00, the absolute dose to the infant during steady-state conditions would be 11.2  μg  kg⁻¹ day⁻¹ and the relative dose 1.8% of the weight-adjusted maternal dose.
Conclusion The study shows that the relative dose to a suckling infant is close to that reported for fluoxetine, and higher than reported for fluvoxamine, paroxetine and sertraline.