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.     

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.     

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.     

The concentration of oxazepam and oxazepam glucuronide in oral fluid, blood and serum after controlled administration of 15 and 30 mg oxazepam

AIMS

To measure and compare the concentration–time profiles of oxazepam and oxazepam glucuronide in blood, serum and oral fluid within the scope of roadside testing.

METHODS

Biological samples were collected from eight male subjects after ingestion of 15 or 30 mg oxazepam on separate dosing occasions with an interval of 7 days. The concentration–time profiles of oxazepam and oxazepam glucuronide were fitted by using a one-compartment model.

RESULTS

For oxazepam and oxazepam glucuronide, the mean oral fluid/blood ratios were 0.05 (range 0.04–0.07) and 0.004 (range 0.002–0.006), respectively. The concentration–time profiles in oral fluid paralleled those in blood.

CONCLUSION

After oral administration of therapeutic doses of oxazepam, concentrations in oral fluid are very much lower than those in blood, and those of oxazepam glucuronide are much lower than those of the parent compound. Nevertheless, assay of oral fluid for oxazepam can be used to detect recent ingestion of the drug in drivers suspected of impaired driving performance.

WHAT IS ALREADY KNOWN ABOUT THE SUBJECT

• Concentration–time profiles of drugs in oral fluid generally run parallel to those in blood.
• In general, oral fluid contains more parent drug than metabolites.
• For some benzodiazepines it has been shown that concentrations are lower in oral fluid than in blood.

WHAT THIS STUDY ADDS

• The concentration–time profile of oxazepam in oral fluid after a single dose of oxazepam runs parallel to blood and is dose dependent.
• Concentration ratios (oral fluid/blood and oral fluid/serum) of oxazepam and oxazepam glucuronide after controlled intake of a single dose of oxazepam are presented.

     

Excretion of noscapine in human breast milk

Summary The excretion of noscapine in human breast milk was studied in 8 lactating women given a single oral dose of 100 or 150 mg after a light breakfast. Serum and milk samples were collected for 24 h after drug intake. Although noscapine is a weak base, only a small amount was excreted in the milk. The median milk/serum ratio was 0.29, range 0.15–0.88. The noscapine dose received by a child during a 24 hour period, when the maternal dose is 50 mg t.i.d., was calculated to be 0.8 (0.4–1.9) µg/kg (median and range).     

Excretion of low molecular weight heparin in human milk

AIMS: The excretion of low molecular weight heparin (LMWH) in breast milk was investigated in 15 lactating mothers after Caesarean section. METHODS: Blood and milk samples were collected before and 3-4 h after once daily routine subcutaneous injection of 2500 IU dalteparin. Anti-Xa activity was measured by an assay utilizing prolonged clotting times in plasma or breast milk as an index of LMWH activity. RESULTS: Plasma anti-Xa activities ranged from 0.074 to 0.308 IU ml(-1) of plasma. Anti-Xa activities in breast milk ranged from < 0.005-0.037 IU ml(-1) of milk. This is equivalent to a milk/plasma ratio of < 0.025-0.224. CONCLUSIONS: Therefore, it appears highly unlikely that puerperal thromboprophylaxis with LMWH has any clinically relevant effect on the nursing infant.     

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.     

Hydroxychloroquine in human breast milk

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

Zolpidem excretion in breast milk

Five, lactating, healthy white women were treated with a single 20 mg tablet of zolpidem 3-4 days after the delivery of a full term baby. The drug was administered at 20.00 h, 30 min after dinner, and milk samples were collected before and 3, 13 and 16 h. Venous blood 5 ml was taken before and 1.5, 3, 13, 16 h after zolpidem administration. The apparent elimination half life, estimated from plasma zolpidem concentrations was 2.6 h. The amount of zolpidem excreted in the milk at 3 h ranged between 0.76 and 3.88 micrograms, which represented 0.004 to 0.019% of the administered dose; no detectable (below 0.5 ng/ml) zolpidem was found in the milk at subsequent sampling times. The ratio of the zolpidem concentrations in breast milk and plasma at 3 h was 0.13. The apparent breast milk clearance of zolpidem, calculated from the ratio of the total amount of zolpidem excreted in milk to its AUC in plasma was 1.48 ml/h. The results show that the excretion of zolpidem in human milk is very low (below 0.02%) and that most of it takes place during the first 3 h following drug intake.     

Piroxicam in breast milk after long-term treatment

Summary The presence of piroxicam in breast milk was determined by HPTLC during initial and long term dosing in 4 women treated for arthritis. Piroxicam appeared in breast milk at about 1–3% of the maternal plasma concentration. No accumulation of piroxicam occurred in milk relative to that in plasma up to 52 days of treatment. Neither piroxicam nor its conjugates were detectable in the urine of one breast-fed infant. The daily dose ingested by the infant was calculated to average 3.5% (maximum 6.3%) of the weight-related maternal dose of piroxicam. It is concluded that a breast-fed infant will be exposed to a very small amount of piroxicam.     

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.     

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.     

奥沙西泮原料及其片剂中有关物质的检查

目的:建立 HPLC 法同时测定奥沙西泮原料及片剂中有关物质的方法。方法:采用 C_(18)柱(150 mm×4.6 mm,5μm),以0.05 mol·L~(-1)磷酸二氢铵-甲醇(45:55,用三乙胺调 pH 8.0)为流动相,流速1.0 mL·min~(-1),检测波长为230 nm。结果:奥沙西泮峰及各杂质峰均能良好分离。杂质 A 浓度在0.092～9.2μg·mL~(-1)范围内与峰面积呈良好的线性关系,回归方程为 Y=67.9X 1.2,r=0.9999,最低检测限为0.13 ng,奥沙西泮中回收率为106.2%,RSD=2.1%(n=6),片剂中回收率为104.2%,RSD 为1.9%(n=6);杂质 B 浓度在0.106～10.6μg·mL~(-1)范围内与峰面积呈良好的线性关系,回归方程为 Y=51.4X-5.6,r=0.9999,最低检测限为0.31 ng,在奥沙西泮中回收率为97.9%,RSD=1.5%(n=6),片剂中回收率为101.5%,RSD 为1.2%(n=6);杂质 C 浓度在0.1～10.0μg·mL~(-1)范围内与峰面积呈良好的线性关系,回归方程为 Y=77.4X 0.28,r=0.9998,最低检测限为0.28 ng,奥沙西泮中回收率为113.1%,RSD=2.5%(n=6),片剂中回收率为110.5%,RSD为2.3%(n=6)。结论:该方法简便、灵敏、专属性好,可用于奥沙西泮原料和制剂中有关物质的检查。     

Transfer of free and conjugated oxazepam across the human placenta

Summary Six women, 13 to 16 weeks pregnant, and 12 women at 38 to 40 weeks gestation, received oral oxazepam about 12 h before legal abortion, by hysterotomy in the former and before elective caesarean section in the latter group. The concentrations of free and conjugated oxazepam in maternal and fetal plasma were determined by gas-liquid chromatography. In early pregnancy the mean ratio between the plasma concentration of total (free + conjugated) drug in the umbilical cord and a maternal vein was 0.6, whereas in late pregnancy the ratio vein was 1.1. Both in early and late pregnancy, the free and glucuronide conjugate of oxazepam were found in the fetus at concentrations which indicated transplacental passage of the parent drug and its metabolite. There was great interindividual variation in the plasma levels both of free and conjugated oxazepam.     

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     

Ampicillin in breast milk during puerperal infections

Summary Low concentrations of ampicillin were found in colostrum/breast milk from 6 mothers treated with pivampicillin 1.05 to 2.1 g daily during the first to eighth day postpartum in the maternity ward. It was calculated that the breast-fed infant could theoretically receive 0.05–0.37% of the dose/kg given to the mother. It is concluded that direct exposure of the breast-fed infant suckling from a mother under treatment with ampicillin or pivampicillin seems to be minimal.     

高效液相色谱法测定乳汁中吗啡浓度

目的:建立高效液相色谱法测定剖宫产妇乳汁中吗啡的浓度.方法:取吗啡镇痛剖宫术产妇乳汁加碱调pH后,用氯仿-异丙醇(80:20)提取,离心,提取液氮气吹干,残渣用甲醇溶解定溶后进样分析;分离柱:μBondapak C18(3.9 mm×300mm,10μm),流动相:0.1 mol·L-1磷酸二氢钠-甲醇(78:22),测定波长233 nm,流速1.04 mL·min-1.结果:乳汁中吗啡在0.5～24 mg·L-1范围内浓度与峰面积比呈良好的线形关系,r=0.999 8,最低检出浓度为0.05 mg·L-1.平均回收率为(99.2±0.8)%,日内及日间平均RSD分别为3.2%和4.9%.结论:该法测定剖宫产妇乳汁中吗啡浓度有良好的准确性,并操作简便,分析时间短,适合剖宫术产妇乳汁中吗啡浓度的测定.     

茵栀黄口服液治疗母乳性黄疸疗效观察

目的观察茵栀黄口服液治疗母乳性黄疸的疗效。方法选择母乳性黄疸100例,随机分为两组,治疗组口服茵栀黄1：3服液,每次5mL,每日2次,对照组采用口服婴儿葡萄糖粉配制成浓度为5％-10％葡萄糖溶液,每次20mL,每日3次。7d为1个疗程。结果治疗组治愈17例,好转29例,无效4例;对照组治愈9例,好转18例,无效23例。两组相比,差异有统计学意义（P〈0．05）。结论茵栀黄口服液治疗母乳性黄疸安全、有效。