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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 671-675 
    ISSN: 1432-1041
    Keywords: famotidine ; histamine H2-receptor antagonist ; diazepam ; hepatic elimination ; tubular secretion ; drug interaction ; cytochrome P450 ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 8 healthy male volunteers the pharmacodynamic responses to a single dose of diazepam and a single dose of procainamide were assessed before and after pre-treatment with the H2-receptor antagonist famotidine in a randomized crossover study. The pharmacokinetics of diazepam and procainamide were also studied, and the binding of famotidine to human liver microsomes was also measured. Cimetidine induced binding changes with a spectral dissociation constant (Ks) of 0.87 mM, whereas famotidine produced no measurable spectral alteration in concentrations up to 4 mM. The elimination half-life (t1/2: 45.6 h) and total plasma clearance (CL: 0.28 ml/min/kg) of diazepam were not significantly altered by famotidine (t1/2=39.0±11.4 h; CL =0.31±0.08 ml/min/kg). Similarly, there was no enhancement of the sedative effect of diazepam by famotidine. The pharmacodynamics and pharmacokinetics of procainamide and N-acetylprocainamide (NAPA), too, were not significantly changed by famotidine: procainamide t1/2 2.9 vs 3.0 h under famotidine and renal clearance (CLR) 436 vs 443 ml/min; and NAPA CLR 195 vs 212 ml/min under famotidine. The data suggest that famotidine, in contrast to cimetidine, does not affect the pharmacokinetics of diazepam (hepatic elimination) or procainamide (tubular secretion). This new H2-receptor antagonist appears to be devoid of an interaction potential for either type of drug elimination.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: ergotamine ; migraine ; bioavailability ; radioimmunoassay ; plasma level ; CSF level ; continuous dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma ergotamine concentrations were determined by radioimmunoassay in 10 healthy subjects after a 2 mg oral dose of ergotamine, administered at 24 h intervals on three consecutive days. After the first dose the mean peak plasma level of 0.35±0.05 (SEM) ng/ml was found 1–2 h after administration. In the samples obtained 2 h after the second and third doses, plasma ergotamine levels did not exceed the first peak value. On the other hand, after the third and last dose the plasma ergotamine began to rise slowly, reaching maximum of 0.70± 0.10 ng/ml on the 6th day after administration. This supports the concept of accumulation of the drug or of immunoreactive metabolites. CSF ergotamine was determined in 4 patients, who underwent lumbar puncture for other diagnostic purposes, 1 to 2 h after the 2 mg oral dose. A concentration of 0.40± 0.03 ng/ml was observed. In seven out of 18 migraine patients who were taking ergotamine preparations daily (mean 11.7 mg/week), ergotamine could not be detected in plasma 1 h after administration of the dose. In the remaining migraine patients, the pattern of plasma ergotamine after both the daily and the test doses was similar to that of the 10 healthy subjects. The results in volunteers and migraine patients suggest notable variation in bioavailability of the drug. It seems that in most subjects there is accumulation or tissue redistribution of ergotamine or its immunoreactive metabolites, although in a significant number of migraine patients who use the drug daily, ergotamine does not appear to be biologically available.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 345-348 
    ISSN: 1432-1041
    Keywords: metoclopramide ; placental transfer ; prolactin ; maternal blood level ; fetal blood level ; amniotic fluid level ; plasma half-life ; plasma TSH ; plasma oestradiol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to study the transplacental transfer of metoclopramide, and its endocrine effects, measurements were made of its concentration in maternal and fetal blood, and in the amniotic fluid, together with maternal and fetal plasma concentrations of prolactin, TSH and oestradiol, during delivery by elective Caesarean section. The drug, 10 mg, was injected i.m. 12 and 2 h and just before the onset of anaesthesia. Metoclopramide was detectable in all the umbilical arterial and venous and amniotic fluid samples, in mean concentrations of 50, 63 and 75 ng/ml, respectively. The mean ratio between the umbilical venous and maternal plasma concentrations was 0.63. Accurate maternal plasma half-lives could not be established, but they must have averaged 2 to 4 h. The high amniotic fluid concentrations and relatively high umbilical venous and arterial concentrations soon after administration suggest that metoclopramide equilibrates relatively rapidly between the mother and fetus. Metoclopramide raised the maternal plasma prolactin levels from 315±128 ng/ml (SD) before therapy to 357±112 ng/ml at the time birth. No statistically significant difference in cord arterial or venous plasma prolactin levels was seen between the control and metoclopramide-treated groups. Metoclopramide did not affect maternal plasma TSH or oestradiol levels. The only change was a slight but significant increase in TSH level in cord blood taken from the umbilical artery after metoclopramide treatment.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 25 (1983), S. 819-823 
    ISSN: 1432-1041
    Keywords: metoclopramide ; breast milk level ; transfer into milk ; prolactin ; thyrotrophin ; maternal blood level ; newborn blood level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and endocrinological effects of metoclopramide were investigated in 5 mothers with deficient lactation and in their children soon after delivery. In addition, the transfer of metoclopramide into breast milk was evaluated in 18 mothers during the 8th to 12th puerperal weeks. Metoclopramide was detected in all the milk samples studied, generally at a higher concentration than in maternal plasma. Metoclopramide was found in plasma from only 1 of the 5 neonates studied. Exposure of the child to metoclopramide, estimated by multiplying the daily breast milk volume by the concentration of metoclopramide in the milk, ranged from 6 to 24 µg/kg/day for the 5 children in the early puerperium to 1 to 13 µg/kg/day for the 18 children during the late puerperium. These quantities are considerably less than the therapeutic dose of 500 µg/kg/day recommended for children. However, the plasma concentration of prolactin in 4 out of 7 neonates sampled taken during administration of metoclopramide to the mother were higher than the highest plasma prolactin level in children of same age of untreated mothers. The plasma concentration of thyrotrophin in the newborns remained within the normal range.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: ergotamine ; radioimmunoassay pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma ergotamine levels were measured in 33 volunteers (subgroups 11, 12 and 10) after a single dose of ergotamine administered by various routes. Ergotamine tartrate was given in doses normally used in the treatment of acute migraine — 2.0 mg orally, 2.0 mg combined with 100 mg caffeine rectally and 0.5 mg i. m. Plasma ergotamine concentrations were determined by radioimmunoassay. The highest and longest lasting levels were found after i. m. administration, the peak concentration being 1.94±0.34 (SEM) ng/ml at 1/2 h. The corresponding maximum concentrations after oral and rectal administration were 0.36±0.08 ng/ml at 2 h and 0.42±0.09 ng/ml at 1 h. In most of the subjects the plasma ergotamine level began to rise again at 24 to 48 h. The cause of the elevation is not known but it might favour possible accumulation of the drug. Absorption from suppositories was at least as good as after oral administration and the former route may therefore be advantageous for migraine patients in whom nausea and vomiting during an attack may prevent efficient oral medication.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 4 (1971), S. 29-31 
    ISSN: 1432-1041
    Keywords: Enzyme induction ; hypercapnia ; hypoxaemia ; tolbutamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The half-life of tolbutamide was investigated in 8 patients with persistent hypercapnia. Both the half-life and tolbutamide concentrations in the blood were significantly lower than in a group of healthy controls. The accelerated metabolism of tolbutamide implied by these observations is probably due to microsomal enzyme induction in the liver, caused both by the prolonged stress of difficulty in breathing and multiple drug treatment. The clinical significance of the findings is discussed.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Pharmaceutical and Biomedical Analysis 11 (1993), S. 1017-1021 
    ISSN: 0731-7085
    Keywords: Liquid chromatography ; acetylation phenotype. ; caffeine metabolites ; urine
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physica B: Physics of Condensed Matter 178 (1992), S. 129-133 
    ISSN: 0921-4526
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physica B: Physics of Condensed Matter 178 (1992), S. 129-133 
    ISSN: 0921-4526
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physica B: Physics of Condensed Matter 194-196 (1994), S. 441-442 
    ISSN: 0921-4526
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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