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  • Analytical Chemistry and Spectroscopy  (2)
  • Key words Mizolastine  (1)
  • clonazepam  (1)
  • imidazopyridine  (1)
  • middle aged subjects  (1)
Material
Years
Keywords
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 585-589 
    ISSN: 1432-1041
    Keywords: clonazepam ; neonates ; convulsions ; therapeutic effect ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eighteen newborns (gestational age 28 to 42 weeks and post-natal age 0.5 to 44 days) suffering from convulsions not controlled by phenobarbital were treated with clonazepam 0.1 mg/kg (8 cases) or 0.2 mg/kg (10 cases) administered by slow intravenous infusion. The plasma half-lives in these ‘phenobarbital pretreated neonates’ were of the same order of magnitude as those reported in adults (20–43 h). Post-natal age did affect clearance, which was 50–70% less than in adults and older children. At the end of the infusion period, plasma clonazepam ranged from 28 to 117 ng/ml in the 0.1 mg/kg group and from 99 to 380 ng/ml in the 0.2 mg/kg group. In the former an immediate therapeutic response was observed in 7 out of 8 cases, and in the latter a significant and somehow delayed effect on convulsion was present only in 6 cases. The data suggest that optimal therapeutic response might already have been achieved with the 0.1 mg/kg dose. Higher doses and toxic concentrations of clonazepam may be detrimental to complete control of seizures and may expose the newborn to an unnecessary risk of adverse events.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1986), S. 231-233 
    ISSN: 1432-1041
    Keywords: betaxolol ; pharmacokinetics ; middle aged subjects ; oral and i.v. administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of betaxolol was studied in 8 middle-aged (40–60 years) subjects after oral (20 mg) and intravenous (10 mg) administration. The principal parameters were almost identical to those observed in young healthy volunteers. The recommended therapeutic regimen, a single daily dose of 20 mg, appears well suited for middle aged, hypertensive patients.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Key words Mizolastine ; H1-receptor antagonist; antihistamine ; skin suction-blister fluid ; histamine-induced wheal and flare
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective:To investigate plasma and skin suction-blister-fluid pharmacokinetics of oral mizolastine in order to determine whether the drug concentration in the fluid of suction-induced skin blisters could better predict the antihistamine activity than the plasma concentration. Setting: Department of Internal Medicine, Université Paris 6. Subjects: Ten healthy male volunteers. Methods: The volunteers (mean age 26.8 years, mean weight 75.8 kg) received a single 10-mg oral dose of mizolastine at 1000 hours. The pharmacokinetic study included 11 plasma and 9 blister fluid samples and blister epidermal-roof specimens. Mizolastine was assayed by high-performance liquid chromatography (HPLC). Each volunteer also received nine intradermal injections of 5 μg histamine. Antihistamine activity was assessed as the post-treatment percentages of changes in the histamine-induced relative wheal and flare areas versus baseline. Results: Mizolastine mean Cmax (SD) and median tmax were, respectively, 380 ng ⋅ ml−1and 0.8 h in plasma, and 21.8 ng ⋅ ml−1 and 10 h in blister fluid. Mizolastine could not be quantified in the epidermis. The maximal histamine-induced relative flare inhibition was 72.5% and was attained at the median time of 3 h post-dosing and therefore was delayed by 2.2 h with respect to the plasma tmax. Mean relative wheal inhibition, although lower, showed the same time profile. A direct relationship could not be found between drug concentrations in blister fluid and antihistamine activity. Simulated concentrations in the peripheral compartment better explain the maximum inhibition effect on flare, observed 3 h post-dosing, with a flatter hysteresis loop obtained when plotting relative flare inhibition versus plasma or blister-fluid drug concentrations. Conclusion: The mizolastine concentrations in the skin suction-blister fluid were not predictive of the antihistamine activity.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 37 (1989), S. 245-248 
    ISSN: 1432-1041
    Keywords: breast milk ; zolpidem ; pharmacokinetics ; imidazopyridine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 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 µg, 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.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0887-6134
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: This paper discusses the possible advantages of thermospray liquid chromatography/tandem mass spectrometry LC/MS/MS for metabolic mapping. The technique was applied to the study of the metabolism of zolpidem, a new hypnotic with an imidazo-pyridine moiety. When compared to other chromatographic/mass spectrometric-based techniques, reversed phase high-performance liquid chromatography coupled with thermospray LC/MS/MS appears to be the fastest method available today for elucidation of unknown metabolic structures, since it allows identification by direct injection of concentrated urine. However, it was noted during the thermospray process that loss of formaldehyde from a hydroxymethyl amide metabolite occurred. This degradation was not observed when this metabolite was analysed by gas chromatography/mass spectrometry following trimethylsilylation.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0306-042X
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Betaxolol, a beta selective adrenoceptor antagonist recently approved for the treatment of hypertension, was determined by monitoring in chemical ionization mode with ammonia the [MH]+ ions of the trimethylsilyl derivatives of the drug and of its internal standard ((2H5)betaxolol). Its pharmacokinetic profile obtained following administration of a 20 mg oral dose was characterized by a half-life of 22 h and a bioavailability of 85%. The main acid metabolite formed by elimination of the isopropylamino group may also be determined as the methyl TMS derivative but methylation with BF3-methanol should be used with caution since it may induce the opening of the cyclopropyl group. The routine electron capture determination procedure was compared to this mass spectrometric method and an excellent correlation was found (r = 0.9974). Both procedures have the same sensitivity (1 ng ml-1). Finally it was observed that under electron impact mode betaxolol trimethylsilyl side chain rearranged to lose TMS—O—CH=CH2; this elimination was confirmed by deuterium labelling studies.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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