首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 46 毫秒
1.
Summary Placental transfer of pinazepam and its metabolite N-desmethyldiazepam was investigated in 25 pregnant women at term. Pinazepam was administered orally as a single (10 mg) dose to 13 women, or in multiple doses of 5 mg daily to 12 women. The dose-delivery interval ranged between 1 and 26 h for the single dose, and the period between the last of the multiple doses and delivery was 1.4 to 24 h. Pinazepam and N-desmethyldiazepam were measured in plasma obtained from the umbilical vein and from the mother, at delivery. Pinazepam was only detectable in plasma after the 10 mg dose. The drug did not reach an apparent equilibrium between fetal and maternal plasma. The average (±SEM) cord/maternal ratio of plasma pinazepam concentrations was 0.64±0.07. N-desmethyldiazepam was detectable on each occasion. Its concentration in the plasma from the cord vein became higher than that in the maternal specimens 1–2 h after administration of the parent drug. Little N-desmethyldiazepam was excreted in breast milk.  相似文献   

2.
Abstract: The binding of digoxin to proteins in plasma and milk was about 20% lower after the addition of the drug to plasma and milk (in vitro) than its binding in plasma and milk from animals administered digoxin parenterally. The mammary excretion of digoxin was examined in the experiments on goats. The concentration of non-protein-bound digoxin in milk was slightly lower than the concentration of non-protein-bound in plasma suggesting a passive diffusion. The amount of digoxin excreted with the milk per day should be far below the dose usually recommended for a newborn child.  相似文献   

3.
Moclobemide excretion in human breast milk.   总被引:1,自引:1,他引:0       下载免费PDF全文
1. Six lactating white women, aged 24-36 years, received a single oral dose of 300 mg moclobemide, between 09.00 h and 11.00 h, 3 to 5 days after the delivery of a full term neonate. 2. Complete milk collections were obtained before, 3, 6, 9, 12 and 24 h after drug administration by means of a breast pump. Venous blood samples were drawn before, and 0.5, 1, 3, 4.5, 6, 9, 12, 24 h post-dosing. 3. Moclobemide, and its major metabolite (Ro 12-8095) were measured in milk and plasma samples using h.p.l.c. The active metabolite (Ro 12-5637) could only be detected in plasma. 4. Moclobemide and its metabolites were not detectable in 24 h plasma samples. Cmax, tmax and t1/2 for moclobemide were (mean +/- s.d.) 2.70 +/- 1.24 mg l-1, 2.03 +/- 1.19 h and 2.26 +/- 0.26 h, respectively. 5. The concentrations of moclobemide and Ro 12-8095 in milk were highest at 3 h after drug administration and the drug and metabolite were not detectable after 12 h. Ro 12-5637 was not detected in any milk sample. The percentages of the dose excreted as moclobemide and Ro 12-8095 were (mean +/- s.d.) 0.057 +/- 0.020% and 0.031 +/- 0.011%, respectively. An average 3.5 kg breast-fed neonate would therefore be exposed to only a 0.05 mg kg-1 moclobemide dose (approximately 1% of the maternal dose on the mg kg-1 basis). The low amount of moclobemide excreted into breast milk is unlikely to be hazardous to suckling infants.  相似文献   

4.
The aim of this study was to determine whether administration of the prodrugs bisacodyl (Bisa) and sodium picosulfate (SPS) leads to excretion of their common active metabolite, bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), in breast milk. Two groups of 8 healthy lactating women who had stopped breast feeding received multiple doses of Bisa or SPS. Plasma, urine, and breast milk were collected and concentrations of free and total BHPM were determined using validated liquid chromatography/mass spectrometry methods. BHPM remained below the limits of detection in breast milk following single- and multiple-dose administration of Bisa and SPS. First, BHPM plasma concentrations were observed after a lag time of about 3 to 4 h and 4 to 5 h following Bisa and SPS administration, respectively. C(max) was attained approximately 5 h after dosing of Bisa and 9 h after dosing of SPS. BHPM did not accumulate after multiple administrations of Bisa and only slightly accumulated following multiple doses of SPS. About 12% and 13% of Bisa and SPS was excreted as BHPM into urine at steady state. BHPM, the active moiety of Bisa and SPS, was not excreted into human breast milk. Hence, use of Bisa or SPS to treat constipation of breast-feeding women is considered well tolerated with regard to exposing infants to BHPM via breast milk.  相似文献   

5.
1. In healthy male volunteers, the absorption, metabolite profiles and excretion of Cbenidipine hydrochloride, a new Ca antagonist, were investigated after oral administration at a dose of 8?mg. 2. C-benidipine hydrochloride was rapidly absorbed, and the plasma concentration of radioactivity and unchanged drug reached a maximum of 71 2 ng eq. ml at 1 1?h and 2 56 ng ml at 0 6?h respectively, and then declined bi-exponentially. The half-life in the elimination phase was 14 7 and 5 3?h respectively. AUC of unchanged drug was low, about 1% of that of radioactivity. 3. Five days after administration,36 4% of the administered radioactivity was excreted in urine and 58 9% in faeces. 4. The metabolite profiles in plasma, urine and faeces were analysed by hplc. At 1?h after administration the predominant metabolites in plasma were M9 and M2, which accounted for 13 8 and 8 2% of the radioactivity respectively, whereas unchanged drug represented 1 2%. Predominant metabolites in urine 12?h after administration were M3 andM8,whichaccountedfor2 22and2 21%oftheadministeredradioactivityrespectively. Metabolites excreted in faeces 120?h after administration were very complex and poorly separated by hplc and could not be characterized: unchanged drug was not detected in the faeces.  相似文献   

6.
The concentrations of CGP 6140 [4-nitro-4'-(N-methyl-piperazinylthiocarbonylamido)-diphenylamine] and of its N-oxide metabolite, CGP 13,231, were measured in plasma and urine after single oral dose of 100-1600 mg of CGP 6140 to 41 fasted Ghanaian patients with Onchocerca volvulus infections. The absorption of CGP 6140 was rapid and its terminal elimination half-life was about 3 h. The plasma concentrations of CGP 6140 were essentially proportional to the dose. A greater variability in plasma concentrations was apparent after the 800 and 1600 mg doses indicating a poor bioavailability of the drug administered in fasting conditions to several patients. In plasma, the concentrations of CGP 13,231 were similar to those of CGP 6140. The amount of CGP 13,231 excreted in urine was 25-40% of the dose of CGP 6140 whereas only 1.5% was excreted as unchanged drug. If a single dose of drug is used for the treatment, the plasma concentration would be maintained for 3-4 h at a high level. At 8 h, the concentration falls to about 10% of the Cmax. If sustained plasma concentrations of the drug are needed for efficacy, twice daily administration would maintain the minimum concentration at about 10% of the Cmax.  相似文献   

7.
Excretion of loratadine in human breast milk   总被引:1,自引:0,他引:1  
The excretion of loratadine, a new nonsedating antihistamine, into human breast milk was studied in six lactating nonpregnant volunteers. Each volunteer received one 40-mg loratadine capsule. Milk and blood were collected before and at specified times (to 48 hours) after dosing. Plasma and milk loratadine concentrations were determined by a specific radioimmunoassay, and those of an active but minor metabolite, descarboethoxyloratadine, by high performance liquid chromatography (HPLC). Breast milk concentration-time curves of both loratadine and descarboethoxyloratadine paralleled the plasma concentration-time curves. For loratadine, the plasma Cmax was 30.5 ng/mL at 1.0 hour after dosing and the milk Cmax was 29.2 ng/mL in the 0 to 2 hour collection interval. Through 48 hours, the loratadine milk-plasma AUC ratio was 1.2 and 4.2 micrograms of loratadine was excreted in breast milk, which was 0.010% of the administered dose. For descarboethoxyloratadine, the plasma Cmax was 18.6 ng/mL at 2.2 hours after dosing, whereas the milk Cmax was 16.0 ng/mL, which was in the 4 to 8-hour collection interval. Through 48 hours, the mean milk-plasma descarboethoxyloratadine AUC ratio was 0.8 and a mean of 6.0 micrograms of descarboethoxyloratadine (7.5 micrograms loratadine equivalents) were excreted in the breast milk, or 0.019% of the administered loratadine dose. Thus, a total of 11.7 micrograms loratadine equivalents or 0.029% of the administered dose were excreted as loratadine and its active metabolite. A 4-kg infant ingesting the loratadine and descarboethoxyloratadine excreted would receive a dose equivalent to 0.46% of the loratadine dose received by the mother on a mg/kg basis.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

8.
Excretion of tiapamil in breast milk.   总被引:1,自引:1,他引:0       下载免费PDF全文
The excretion of tiapamil in breast milk was studied in six lactating mothers (3-7 days post partum) following a single oral 600 mg dose of the drug. The milk/plasma ratio of tiapamil derived from the areas under the plasma and milk concentration-time curves was 0.44 +/- 0.10 mean +/- s.d.). Assuming an intake of 350 ml of milk during a dosing interval of 12 h, the newborn would be exposed at the maximum to 0.053 mg tiapamil. This small amount does not represent a risk for the baby.  相似文献   

9.
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.  相似文献   

10.
Summary The concentrations of lormetazepam and its glucuronide in plasma and milk were determined during administration of 10 daily doses of lormetazepam 2 mg (2 tablets of NOCTAMID® - 1) to five mothers delivered by Caesarian section. Their babies were breast-fed throughout the study, and the plasma levels of lormetazepam and its glucuronide were determined three times in the babies. At 12 and 24h after administration, the plasma level of lormetazepam was about 3.5 ng/ml and 1.8 ng/ml in mothers, and below 0.09 ng/ml in the children. In milk the lormetazepam concentration was below 0.2 ng/ml. The plasma level of glucuronide varied between 24 ng/ml at 12h and 11 ng/ml 24h after administration. Almost no accumulation of unchanged lormetazepam was observed (factor: 1.3). The ratio of the levels of lormetazepam in milk and plasma was estimated to be below 0.06, and for the glucuronide the ratio was 0.04. The quantity of free and conjugated active ingredient transferred to the children via breast milk was calculated to be at most 100 ng/kg, corresponding to 0.35% of the maternal dose, which is regarded as tolerable.  相似文献   

11.
AIMS: To compare the duration of the residual hypnotic and sedative effects of zaleplon with those of zolpidem and placebo following nocturnal administration at various times before morning awakening. METHODS: Zaleplon 10 mg, zolpidem 10 mg, or placebo was administered double-blind to 36 healthy subjects under standardized conditions in a six-period, incomplete-block, crossover study. Subjects were gently awakened and given medication at predetermined times 5, 4, 3, or 2 h before morning awakening, which occurred 8 h after bedtime. When the subjects awoke in the morning, a battery of subjective and objective assessments of residual effects of hypnotics was administered. RESULTS: No residual effects were demonstrated after zaleplon 10 mg, when administered as little as 2 h before waking, on either subjective or objective assessments, whereas zolpidem 10 mg showed significant residual effects on DSST and memory (immediate and delayed free recall) after administration up to 5 h before waking and choice reaction time, critical flicker fusion threshold and Sternberg memory scanning after administration up to 4 h before waking. Residual effects of zolpidem were apparent in all objective and subjective measurements when the drug was administered later in the night. CONCLUSIONS: The present results demonstrate that zaleplon at the dose of 10 mg is free of residual hypnotic or sedative effects when administered nocturnally as little as 2 h before waking in normal subjects. In contrast, residual effects of zolpidem are still apparent on objective assessments up to 5 h after nocturnal administration, longer than has been reported from studies involving daytime administration.  相似文献   

12.
The disposition and metabolism of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), a new agent with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic properties, was studied in rats, dogs, and rhesus monkeys. [3H]benzene-MK-801 was administered orally at a dose of 1 mg/kg. MK-801 was measured in plasma by GLC using a nitrogen detector; the overall sensitivity of the method was 3 ng/ml. Radioactivity was excreted mainly in urine of dogs and monkeys but fecal excretion in rats was also extensive. The apparent plasma t1/2 of MK-801 in the rat and dog was approximately 1 hr. Maximal plasma levels of MK-801 in the rat, dog, and monkey were 46 (0.5 hr), 16 (0.25 hr), and 10 (2 hr) ng/ml, respectively. Radioactivity was extensively excreted in rat bile and was widely distributed among various tissues. Major metabolites of the drug in rat and dog urine were the 2- and 8-hydroxy analogs (rat) and the N-hydroxy derivative (dog).  相似文献   

13.
Knowledge of pharmacokinetics and the use of a mechanistic-based approach can improve our ability to predict the effects of pregnancy for medications when data are limited. Despite the many physiological changes that occur during pregnancy that could theoretically affect absorption, bioavailability does not appear to be altered. Decreased albumin and alpha(1)-acid glycoprotein concentrations during pregnancy will result in decreased protein binding for highly bound drugs. For drugs metabolised by the liver, this can result in misinterpretation of total plasma concentrations of low extraction ratio drugs and overdosing of high extraction ratio drugs administered by non-oral routes. Renal clearance and the activity of the CYP isozymes, CYP3A4, 2D6 and 2C9, and uridine 5'-diphosphate glucuronosyltransferase are increased during pregnancy. In contrast, CYP1A2 and 2C19 activity is decreased. The dose of a drug an infant receives during breastfeeding is dependent on the amount excreted into the breast milk, the daily volume of milk ingested and the average plasma concentration of the mother. The lipophilicity, protein binding and ionisation properties of a drug will determine how much is excreted into the breast milk. The milk to plasma concentration ratio has large inter- and intrasubject variability and is often not known. In contrast, protein binding is usually known. An extensive literature review was done to identify case reports including infant concentrations from breast-fed infants exposed to maternal drugs. For drugs that were at least 85% protein bound, measurable concentrations of drug in the infant did not occur if there was no placental exposure immediately prior to or during delivery. Knowledge of the protein binding properties of a drug can provide a quick and easy tool to estimate exposure of an infant to medication from breastfeeding.  相似文献   

14.
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, Cmax 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  相似文献   

15.
A single dose of arbaprostil-11 beta-3H (4 micrograms/kg) was administered orally to male rats. A maximum plasma radioactivity concentration equivalent to 2.5 to 2.8 nanograms of the prostaglandin per ml was reached at 30 minutes and was maintained until 120 minutes after drug administration. The plasma drug disappearance half-life was 2.6 hours. These results along with data from tissue distribution studies suggested a rapid uptake of radiolabeled arbaprostil by the glandular stomach tissue followed by an apparent zero-order release of drug-related radioactivity from this tissue "reservoir" into the plasma. Drug-related radioactivity was excreted rapidly, with 96 to 99% of the urinary excretion and 82 to 97% of the fecal excretion being completed within 24 hours. A total of 49.6 +/- 3.5% of the orally administered dose was excreted in the urine and 46.7 +/- 3.9% in the feces. No radioactive residues were detected in the animals at the end of the 120 hour specimen collection period. The metabolic stability of the 11 beta-tritium label and the suitability of arbaprostil-3H for use in human studies was demonstrated.  相似文献   

16.
The plasma pharmacokinetics, and the urinary excretion, of terbinafine and its five main metabolites have been investigated after a single oral dose administration of 125 mg to 16 healthy subjects. In plasma, the highest concentrations are observed for the two carboxybutyl metabolites, with a predominance for the carboxybutylterbinafine. For this metabolite, as compared to terbinafine, the Cmax and AUC are 2.4 and 13 times higher respectively. The demethylterbinafine presents a plasma profile close to that of terbinafine. The two hydroxy metabolites are only found as glucuronide and are of minor importance. The apparent terminal half-lives of terbinafine, demethylterbinafine, and the two carboxy metabolites appear to be similar (~ 25h). As compared to the plasma concentration of total radioactivity observed after a single oral administration of the same dose of 14C-terbinafine, the parent drug and these five metabolites, account for more than 80% of the total radioactivity in plasma over the 0–48 h interval following administration. In urine, the major metabolite is demethylcarboxybutylterbinafine, which amounted to about 10% of the administered dose. Terbinafine and demethylterbinafine are only excreted as trace amounts in urine. Carboxybutylterbinafine and the two hydroxy metabolites are excreted in the range of 0.5–2% either as glucuronides or free. Urinary excretion over the 0–48h interval of terbinafine and of the five metabolites amounted to about 14% of the administered dose. This is far below the level of total radioactivity measured in urine over the same interval (~ 57%), after administration of 14C-terbinafine. This shows in contrast to plasma, that numerous other metabolites are present in urine.  相似文献   

17.
1 Paracetamol was administered to nursing mothers. The drug passed rapidly into milk and the milk:plasma concentration ratio was approximately unity. 2 The estimated maximum dose to the neonate was 1.85% of the weight-adjusted maternal oral dose of paracetamol 1.0 g. Recovery of paracetamol was greater from the breast from which samples were taken frequently than from the breast which was sampled only once. 3 Paracetamol, its glucuronide, sulphate, cysteine and mercapturate conjugates were found in the urine of the neonates although only the parent drug was detected in breast milk. 4 The neonates excreted significantly greater proportions of unchanged paracetamol (P less than 0.01) and significantly lesser proportions of paracetamol sulphate (P less than 0.001) than did healthy volunteers aged 11-80 years who received a therapeutic dose of paracetamol. 5 The findings are compatible with a deficiency of sulphate conjugation by the neonate.  相似文献   

18.
Summary The concentrations of mepindolol in plasma and milk of five breastfeeding mothers were determined after 1 and 5 daily doses of mepindolol sulphate 20 mg. In the newborns plasma levels were measured once on the first and fifth days of the study. The mean maternal plasma concentration of mepindolol 2 h after administration was 52 ng/ml both after 1 and 5 doses; in the milk 18 and 22 ng/ml the corresponding concentrations were. The average plasma/milk drug concentration ratio was 2.6±1.6. Plasma levels in the newborns were below the detection limit of 1 ng/ml, except for one baby in whom 2 and 5 ng/ml, respectively, were found 4 h after one and five maternal doses.  相似文献   

19.
The disposition and metabolism of 14C-labeled fluconazole (100 microCi) was determined in three healthy male subjects after administration of a single oral capsule containing 50 mg of drug. Blood samples, total voided urine, and feces were collected at intervals after dosing for up to 12 days post-dose. Pharmacokinetic analysis of fluconazole concentrations showed a mean plasma half-life of 24.5 hr. Mean apparent plasma clearance and apparent volume of distribution were 0.23 ml/min/kg and 0.5 liter/kg, respectively. There was no evidence of any significant concentrations of metabolites circulating either in plasma or blood cells. Mean total radioactivity excreted in urine and feces represented 91.0 and 2.3%, respectively, of the administered dose. Mean excretion of unchanged drug in urine represented 80% of the administered dose; thus, only 11% was excreted in urine as metabolites. Only two metabolites were present in detectable quantities, a glucuronide conjugate of unchanged fluconazole and a fluconazole N-oxide, which accounted for 6.5 and 2.0% of urinary radioactivity, respectively. No metabolic cleavage products of fluconazole were detected.  相似文献   

20.
1. The excretion of indomethacin into breast milk and subsequent exposure of infants was studied in 16 women and seven of their infants. The median milk:plasma ratio in seven patients where there were measurable drug concentrations in both milk and plasma was 0.37. 2. Total infant dose, assuming a daily milk intake of 150 ml kg-1 and 100% absorption, ranged from 0.07% to 0.98% (median = 0.18%) of the weight adjusted maternal dose. 3. Plasma samples were obtained in seven infants. In six of these, indomethacin concentrations were below the sensitivity of the assay (less than 20 micrograms l-1), while one infant had a plasma indomethacin concentration of 47 micrograms l-1. 4. No adverse effects due to indomethacin were reported in the infants.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号