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  • 1
    Electronic Resource
    Electronic Resource
    Single and multiple dose kinetics of clobazam, and clinical effects during multiple dosage (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 499-503 
    Details
    ISSN: 1432-1041
    Keywords: benzodiazepines ; clobazam ; desmethylclobazam ; pharmacokinetics ; sedation ; accumulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen healthy volunteers, aged 19 to 62 years, took a single 20-mg oral dose of clobazam and the serum concentrations of clobazam and desmethylclobazam were measured for the following 7 days. The mean kinetic variables for clobazam were: volume of distribution 1.31/kg, elimination half-life 24 h, total clearance 0.47 ml/min/kg. 13 of the volunteers then took clobazam 5 mg twice daily for 22 consecutive days. Serum concentrations were measured during and after this period. Both clobazam and desmethylclobazam showed slow and extensive accumulation, their steady-state kinetics being entirely consistent with those observed after single doses. Elimination of both compounds after termination of treatment was equally slow. Clinical self-rating of morning sedation indicated a significant increase over baseline in subjective perception of sedation during the treatment period, and this effect persisted into the washout period. However, sedation did not increase in parallel with accumulating levels of clobazam and desmethylclobazam, probably due to functional adaptation or tolerance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542148
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  • 2
    Electronic Resource
    Electronic Resource
    Disposition of clotiazepam: Influence of age, sex, oral contraceptives, cimetidine, isoniazid and ethanol (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 55-59 
    Details
    ISSN: 1432-1041
    Keywords: clotiazepam ; drug interaction ; cimetidine ; isoniazid ; ethanol ; pharmacokinetic ; oral contraceptives ; age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Factors influencing the disposition of clotiazepam in man were evaluated in a series of pharmacokinetic studies in healthy volunteers given a single 5 mg dose. Old age caused an increased volume of distribution of clotiazepam in women, and its clearance tended to be reduced in elderly men. Use of oral contraceptives, cimetidine, isoniazid or a single dose of ethanol had no significant effect on the kinetics of clotiazepam. Although clotiazepam is biotransformed by microsomal oxidation, its clearance appears to be relatively uninfluenced by factors known to alter the clearance of other oxidized benzodiazepines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546709
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  • 3
    Electronic Resource
    Electronic Resource
    Effect of dose on bioavailability of oral digoxin (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 53-55 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; bioavailability ; dose-dependency ; urinary excretion ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine healthy volunteers received single 0.25, 0.5, 1.0, 1.5, and 2.0 mg doses of oral digoxin tablets in random sequence on five occasions separated by at least 4 weeks. Urinary excretion of immunoassayable digoxin was determined from 8 consecutive 24 h urine samples collected after each dose. Mean values of cumulative urinary excretion of digoxin at the 5 doses were: 40.9, 35.6, 36.4, 34.1, and 33.5% of the dose (F=0.64; d. f.=4.32; N. S.). Mean values of urinary excretion half-life were: 2.48, 2.03, 2.20, 2.07, and 1.87 days (F=2.87; d. f.=4.32;p=0.05). Thus, the bioavailability of orally administered digoxin tablets in healthy volunteers is dose-independent over an 8-fold range of doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558384
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  • 4
    Electronic Resource
    Electronic Resource
    Intravenous quinidine in congestive cardiomyopathy (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 173-176 
    Details
    ISSN: 1432-1041
    Keywords: cardiomyopathy ; quinidine ; left ventricular performance ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight male patients with compensated congestive cardiomyopathy received single 300-mg doses of intravenous quinidine by 15-min infusion. Left ventricular (LV) performance was evaluated by echocardiography at multiple points in time during the next 24 h. Quinidine kinetics and protein binding were determined from multiple serum samples drawn for up to 36 h after dosage. LV function was not impaired. Instead, quinidine transiently increased ejection fraction (mean: +39%) and rate of circumferential shortening (mean: +46%). Endsystolic and end-diastolic LV internal diameter likewise were decreased (means: −13% and −7%). Blood pressure and ventricular rate were not significantly altered. Compared to 8 healthy controls matched for age, sex, and weight, quinidine volume of distribution among patients was smaller (means: 2.27 vs 1.90 l/kg), as was total quinidine clearance (3.49 vs 2.84 ml/min/kg); however, differences were not statistically significant. Well-controlled, slow intravenous infusion of quinidine does not impair LV performance and is safe for patients with compensated congestive cardiomyopathy. However, such patients may have reduced quinidine clearance and hence require lower doses than expected based on age and weight.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561944
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of oxaprozin in women receiving conjugated estrogen (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 105-108 
    Details
    ISSN: 1432-1041
    Keywords: oxaprozin ; NSAIA ; conjugated estrogens ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of a single 1200 mg oral dose of oxaprozin, a nonsteroidal antiinflammatory agent of the propionic acid class, was studied in 22 healthy female volunteers aged 21 to 64 years. Eleven subjects had been taking a conjugated estrogen preparation for at least 3 months; the other 11 subjects served as control women who were not taking conjugated estrogens. Mean pharmacokinetic variables in control and conjugated estrogen groups were: volume of distribution, 15.1 vs 14.11; elimination half-life, 59.8 vs 54.2 h; clearance, 3.2 vs 3.1 ml/min; peak plasma concentration, 84.8 vs 90.7 µg/ml, respectively. None of the differences were significant. However, the time of peak concentration (8.9 vs 4.0 h) was significantly longer in the control group than in the conjugated estrogen group, respectively (p〈0.05). Oxaprozin clearance, accomplished by a combination of oxidation and conjugation, is unimpaired by coadministration of conjugated estrogens.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00555518
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  • 6
    Electronic Resource
    Electronic Resource
    Actual versus reported benzodiazepine usage by medical outpatients (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 383-388 
    Details
    ISSN: 1432-1041
    Keywords: benzodiazepines ; population usage and survey ; unreported usage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Benzodiazepines are widely prescribed, and in 1979 almost 10% of the adult population was taking them. Prior studies of outpatient usage of benzodiazepines have relied on survey or prescription data, which may be confounded by noncompliance. To determine the actual use of benzodiazepines, plasma benzodiazepine concentrations were measured in 225 consecutive outpatients from a university cardiology outpatient service. Self reports indicated that the great majority of the patients (191) were taking at least one medicine, and 70 reported being on a psychotropic drug. Seventy-seven patients reported taking benzodiazepines, the majority being on bromazepam (20), diazepam (26) or oxazepam (19). In 25 of those 77 patients, the reported drug could not be detected in plasma. Conversely, in 10 of the 225 patients, benzodiazepines which were not reported were detected (diazepam or flurazepam). Of those taking benzodiazepines, many had a low concentration, suggesting intermittent rather than regular use. Thus, many patients for whom benzodiazepines are prescribed take them irregularly, and a small group uses them without reporting their prescription. These findings have implications for the clinical presentation of illness and for the possibility of drug interactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543974
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  • 7
    Electronic Resource
    Electronic Resource
    Effect of cirrhosis and renal failure on the kinetics of clotiazepam (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 89-92 
    Details
    ISSN: 1432-1041
    Keywords: clotiazepam ; liver cirrhosis ; renal insufficiency ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of a single 5-mg oral dose of the thienodiazepine clotiazepam was evaluated in a series of patients with biopsy-proven cirrhosis, and in patients with renal insufficiency requiring maintenance hemodialysis, compared to healthy matched controls. Clotiazepam volume of distribution (Vz) was significantly smaller in cirrhotic patients than in controls (1.83 vs 2.57 l/kg), and total clearance was likewise reduced (2.15 vs 3.15 ml/min/kg). Elimination half-life was similar between groups (10.0 vs. 10.2h). There were no significant differences between renal failure and control patients in clotiazepam Vz, oral clearance, or elimination half-life. Thus cirrhosis is associated with reduced clearance of clotiazepam, probably due to impairment of its microsomal oxidation. However clotiazepam disposition is not significantly altered in dialysis-dependent renal insufficiency patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614202
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  • 8
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    Single and multiple dose kinetics of clobazam, and clinical effects during multiple dosage (1984)
    Springer
    Details
    Publication Date: 1984-01-01
    Print ISSN: 0031-6970
    Electronic ISSN: 1432-1041
    Topics: Chemistry and Pharmacology , Medicine
    Published by Springer
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  • 9
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    Intravenous quinidine in congestive cardiomyopathy (1981)
    Springer
    Details
    Publication Date: 1981-02-01
    Print ISSN: 0031-6970
    Electronic ISSN: 1432-1041
    Topics: Chemistry and Pharmacology , Medicine
    Published by Springer
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  • 10
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    Actual versus reported benzodiazepine usage by medical outpatients (1987)
    Springer
    Details
    Publication Date: 1987-01-01
    Print ISSN: 0031-6970
    Electronic ISSN: 1432-1041
    Topics: Chemistry and Pharmacology , Medicine
    Published by Springer
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