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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. 237-241 
    ISSN: 1432-1041
    Keywords: Ambroxol ; Uricosuric effect ; uric acid clearance ; creatinine clearance ; hypoxanthine ; diurnal rhythm ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ambroxol is known to promote bronchial secretion and is used as an expectorant. Previous studies had suggested that high doses of ambroxol could reduce the plasma uric acid concentration. The present study was undertaken to confirm this finding, to determine its dose-response relationship and to identify the underlying mechanism of action. Using a placebo-controlled, double-blind parallel group design, 48 healthy male volunteers were randomly allocated to receive placebo b.d. and ambroxol 125 mg b.d., 250 mg b.d. or 500 mg b.d. (12 subjects per group). The subjects were hospitalised during a dietary run-in period of 3 days (Days -3 to -1) and a treatment period of 5 days (Days 1 to 5). On Day -1 (baseline) and Days 1 to 5, all urine was collected and blood samples were taken for the analysis of uric acid, creatinine, xanthine and ambroxol. The measurements were repeated four days after treatment had closed. Steady state plasma concentrations of ambroxol (trough levels) were reached after 2 or 3 days and were linearly related to dose. Ambroxol induced a significant, dose-dependent, reduction in plasma uric acid (250 mg b.d. about 20%; and at 500 mg b.d. about 30%). The diurnally fluctuating uric acid clearance was dose dependently increased and there was no notable effect on creatinine clearance. Plasma hypoxanthine levels were not affected by ambroxol. No severe adverse events were reported and no drug induced changes in the clinical laboratory values were observed. It is concluded that ambroxol has an uricosuric action following oral administration of higher doses (250 mg-500 mg b.d.) and it is well tolerated.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: ipratropium bromide ; radioceptor assay ; pharmacokinetics ; inhalation ; systemic administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single doses of ipratropium bromide were administered intravenously, orally and by slow inhalation to ten healthy male volunteers. The plasma level after oral administration followed a low but broad plateau persisting for several hours. After i.v. administration the kinetic parameters were: Vc=25.9 l, Vα=13.1 l, Vβ=338 l, $$t_{{1 \mathord{\left/ {\vphantom {1 {2_\alpha }}} \right. \kern-\nulldelimiterspace} {2_\alpha }}} = 3.85\min $$ , $$t_{{1 \mathord{\left/ {\vphantom {1 {2_\beta }}} \right. \kern-\nulldelimiterspace} {2_\beta }}} = 98.4\min $$ , AUC=15.0 h · ng/ml, kel=11.8 l/h and total clearance is 2325 ml/min. The bioavailability was 3.3% (range 0.9–6.1%) on comparing the plasma AUCs following i.v. and 20 mg oral administration. The cumulative renal excretion (0–24 h) after i.v. administration was compared with that after oral administration and inhalation. Following oral administration, the apparent systemic availability was around 2%, and after inhalation it was 6.9%. In comparison with oral placebo administration, only after i.v. administration was there a significant change in heart rate (from 63.7 to 90.2 beats/min). The systolic blood pressure rose from 115.1 to 119.6 mm Hg and the diastolic blood pressure from 68.3 to 78.3 mm Hg.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: oxitropium bromide ; pharmacokinetics ; radioreceptor assay ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Oxitropium bromide (OXBR) is a new anticholinergic drug, which is expected to be useful in the treatment of nocturnal asthma. The only pharmacokinetic data were obtained with the14C-labelled compound. A sensitive radioreceptor assay for the determination of unlabelled OXBR in plasma was developed, based on competition between OXBR and3H-N-methylscopolamine for binding to muscarinic receptors. OXBR was isolated from plasma by ion-pair extraction and re-extraction. Active metabolites present in significant amounts might interfere in the assay, but this was not the case for OXBR metabolites. Detection limits were 300 pg·ml−1 and 3 ng·ml−1 for plasma and urine, respectively. For the latter no extraction step was required. The single dose pharmacokinetics of OXBR was studied following inhalation (3 mg), oral (2 mg) and i.v. (1 mg) administration to 12 men, following an open, cross-over design. After i.v. administration the kinetic parameters were: Vc 38.4 l; t1/2α 5.3 min; t1/2β 142 min; AUC 8.9 h·ng·ml−1; renal excretion 50.2%, k10 3.5 l·h−1 and total clearance 1874 ml/min. The apparent bioavailabilities were 0.48% and 12.4% by the oral and inhalation routes, respectively, based on the cumulative renal excretion. There were moderate adverse reactions due to the anticholinergic properties of the drug.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 41 (1986), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The bronchospasmolytic effects of 40 μg ipratropium bromide (Atrovent®) given either as an aerosol (2 puffs of 20 μg) or as a powder inhalation were compared in a double-blind cross-over study. Following a randomisation list the drug was given on 2 successive days to 20 patients with stable bronchospasm in whom it had previously been shown that the bronchial obstruction was reversible after administration of 40 μg ipratropium bromide as an aerosol (with an increase over- the baseline value of the FEV1 of at least 15% 1 h after drug administration). The effects of the two presentations of ipratropium bromide were followed by respiratory function tests from 15 min to 6 h after administration of the drug. With both formulations excellent bronchospasmolytic effects were noted in each of the parameters measured. The peak of the effects was noted approximately 1 h alter the inhalations. Six hours later there was still a significant improvement in comparison with the baseline values. There was no significant difference between the results with the two different formulations. Inhalation powder of ipratropium bromide was well tolerated and there were no complaints of irritation or coughing. It would appear, therefore, to be a valuable alternative to the pressure aerosol.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 3 (1981), S. 800-809 
    ISSN: 1573-739X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The photochemical activity of nitrazepam, clonazepam and flunitrazepam has been investigated. These closely structurally related compounds decompose photochemically in an oxygen-poor medium, resulting in photoreductive dimerisation and photoreduction of the nitro-group to successively the nitroso, the hydroxylamino and finally the amino analogue of the nitro-compound. The photoreductive dimerisation compound is a result of a coupling reaction between the respective nitroso and hydroxylamino derivatives. In an oxygen-rich medium, however, the 7-nitro-1,4-benzodiazepines are relatively photostable. It appears that the quenching of excited clonazepam and nitrazepam leads exclusively to the formation of singlet molecular oxygen, while in the case of flunitrazepam, beside singlet molecular oxygen, also another reactive oxygen-dependent species is formed. In addition the photochemical activity of methylnitrazepam, methylclonazepam and desmethylflunitrazepam has been investigated. It appears that a relationship exists between the 7-nitro group in the 1,4-benzodiazepine nucleus and the photochemical behaviour.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 3 (1981), S. 1205-1211 
    ISSN: 1573-739X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Conclusie Het gebruikte micro-organisme blijkt bijzonder geschikt te zijn om de relatie structuur-fotobiologische activiteit te bestuderen. Bij het voorspellen van een eventueel risico bij therapeutisch gebruik, zal men zich bewust moeten zijn van het feit dat de experimentele resultaten verkregen zijn met een micro-organisme. Vanwege het grote verschil in celstructuur is een directe extrapolatie naar de mens dan ook niet mogelijk. Gelet op het feit dat chloordiazepoxide zowel bij de muis als bij therapeutisch gebruik bij de mens fototoxiciteit kan veroorzaken, zou een indicatie kunnen zijn dat zich hier een vergelijkbaar type van fotobiologische activiteit voordoet als in het bovengenoemde micro-organisme.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 3 (1981), S. 828-832 
    ISSN: 1573-739X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Pharmacy world & science 2 (1980), S. 547-556 
    ISSN: 1573-739X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract By labelling chlordiazepoxide and diazepam with14C it was possible to follow quantitatively the photochemical decomposition of these compounds. It was found for chlordiazepoxide that the wavelength of light does not determine the character, but only the concentrations of the products formed. On irradiation of chlordiazepoxide, dissolved in methanol or methanol-water (pH=7.4), an oxaziridine is formed, which is subsequently converted into a quinoxaline and a benzoxadiazocine derivative. However, by irradiation in the presence of glutathione, the rate of decomposition is increased and the scheme is completely changed. Instead of the quinoxaline and the benzoxadiazocine derivative, the reduced form of chlordiazepoxide and a conjugate are formed. It was established that the oxaziridine, the first photoproduct of chlordiazepoxide, reacts spontaneously with glutathione at room temperature without light. On irradiation of diazepam, dissolved in methanolwater (pH=7.4), with light of 300 nm a benzophenone derivative is the only decomposition product, while with light of 254 nm also a quinazoline derivative is formed as a minor product. With methanol as solvent (λ=254 nm) the concentration of the products formed is strongly influenced, quinazoline derivatives become the main products and the benzophenone derivative a minor product.
    Type of Medium: Electronic Resource
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