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  • pharmacokinetics  (6)
  • atenolol  (3)
  • antidiabetic drugs  (2)
  • 1
    Digitale Medien
    Digitale Medien
    Observations on the efficacy and pharmacokinetics of sotalol after oral administration (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 367-372 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Sotalol ; β-adrenoceptor blocking drugs ; exercise tachycardia ; efficacy ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of sotalol after oral administration were measured on the tachycardia induced by strenuous exercise in normal subjects. Plasma sotalol levels were also determined. The oral administration of sotalol (50, 100, 200 and 400 mg) to 6 subjects produced a progressive reduction in the tachycardia induced by severe exercise. This was similar to the effects of 25, 50, 100, 200, 400 and 800 mg given to different subjects. Each increase in sotalol dose produced a successively greater reduction in exercise tachycardia. This did not appear to be maximum even with 800 mg. Oral sotalol was rapidly absorbed and produced peak blood levels in 2 – 3 hours. The plasma levels of sotalol measured 2 hours after the oral administration of 25 to 800 mg showed never more than a six-fold variation between different subjects. The half-life of sotalol in plasma was 12.7 ± SE 1.6 hours. There was a significant correlation between the logarithm of the plasma sotalol concentration and the percentage reduction of exercise heart rate. It is concluded that the oral administration of sotalol either once or twice daily (depending on dose level) will provide satisfactory 24-hour blockade of β-adrenoceptors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00606550
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  • 2
    Digitale Medien
    Digitale Medien
    The effects of chronic dosing on the β1 and β2-adrenoceptor antagonism of betaxolol and atenolol (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 467-471 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Betaxolol ; atenolol ; nadolol ; cardioselectivity ; β-adrenocepter antagonism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Six normal subjects were given once daily treatment for 15 days with placebo (PL), betaxolol 10 mg (B10), 40 mg (B40); atenolol 100 mg (A100); and nadolol 40 mg (N40). Measurements of β1-adrenoceptorblockade (reduction of exercise heart rate) and of β2-adrenoceptor-blockade (attenuation of isoprenaline induced finger tremor) were made after the first, eighth and fifteenth doses of each drug. Plasma concentrations showed dose related increases between 10 mg and 40 mg doses of betaxolol, and there was significant drug accumulation at steady state compared with after single dosing. The reduction in exercise heart rate (EHR) with B10 was less in comparison with all other treatments. There were no significant differences in effects between single and chronic-dosing for any of the treatments (% reduction EHR compared with placebo, on days 1 and 15): B10 (18.2, 19.0), B40 (28.6, 26.5); A100 (22.7, 23.1); N40 (26.6, 23.8). Dose-ratios for attenuation of isoprenaline-induced finger tremor (IT100) were significantly greater with B40 compared with B10 or A100 (no dose-ratio for finger tremor could be calculated for N40). There were no differences between single and chronic-dosing (IT100 dose-ratios on days 1 and 15): B10 (3.0, 2.5), B40 (4.4, 5.3); A100 (3.0, 3.0). The attenuation of isoprenaline-induced chronotropic response (IH25) by N40 was significantly greater in comparison with all other treatments. IH25 dose-ratios (on days 1 and 15) were as follows: B10 (2.8, 3.6), B40 (5.1, 5.8); A100 (3.6, 3.6); N40 (19.0, 17.4). Thus, despite drug accumulation after chronic-dosing, there was no evidence of any increase in either β1 or β2-adrenoceptor antagonism at steady-state in comparison with after single-dosing. The apparent dissociation between plasma concentration and β-adrenoceptor antagonism after chronic-dosing my be a consequence of β-adrenoceptor up-regulation, resulting in partial attenuation of β-blockade.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315224
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  • 3
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of sotalol during pregnancy (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 521-524 
    Details
    ISSN: 1432-1041
    Schlagwort(e): sotalol ; beta-adrenoceptor antagonist ; pregnancy ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Sotalol, a beta-adrenoceptor blocking drug, was administered to 6 healthy pregnant volunteers between 32–36 weeks gestation and when at least 6 weeks post-partum. On both occasions, each volunteer was given sotalol 100 mg intravenously and 400 mg orally in randomised order with at least a 1 week washout period between. Plasma samples were analysed for sotalol using a fluorometric method and the pharmacokinetic profiles investigated. The systemic clearance of sotalol was significantly greater in the antenatal period (2.4±0.3 ml/min/kg) than in the post-natal phase (1.5±0.1 ml/min/kg). The apparent volume of distribution was similar in the two periods: the elimination half-life was 6.6±0.6h ante-natally and 9.3±0.7h post-natally after intravenous drug but the trend for faster elimination was not significant. The elimination half-life after oral administration (about 10h) and bioavailability (about 90%) were not altered significantly by pregnancy. It is suggested that the more rapid clearance of sotalol in pregnancy may be due to increases in renal plasma flow and glomerular filtration rate.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609896
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  • 4
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of propranolol during pregnancy (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 583-587 
    Details
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; pregnancy ; beta-adrenoceptor antagonist ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Propranolol, a beta-adrenoceptor blocking drug, was administered to 6 healthy pregnant volunteers between 32 and 36 weeks gestation and when at least 6 weeks postparum. On both occasions, subjects were given propranolol 120 mg orally or 10 mg intravenously in randomised order with a minimum washout period of 1 week. Propranolol was assayed in plasma by gas-liquid chromatography with electron-capture detection and the pharmacokinetic parameters were investigated. There were no significant alterations in elimination half-life, clearance or apparent volume of distribution per kilogram antenatally compared with postnatally: bioavailability was also unchanged. It is concluded that the disposition of propranolol is not altered during pregnancy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00556896
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  • 5
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of a microcrystalline theophylline preparation in patients with chronic obstructive airways disease (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 29-33 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Microcrystalline theophylline ; chronic obstructive airways disease ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma theophylline concentrations have been measured in 9 patients with chronic obstructive airways disease following the oral administration of a microcrystalline theophylline preparation. Some measurements of FEV1 were also made. Four patients were given 375 mg as a single dose and then subsequently 375 mg stat and 125 mg 4 times daily for 3 days, (Group I). A further 5 patients took 250 mg as a single dose and then 250 mg 4 times daily for 3 days, (Group II). In both groups, following the single dose and again after the last dose of chronic administration, blood samples were obtained at frequent intervals up to 24 h for plasma drug estimation. During the 3-day course, blood samples were drawn before and 2 h after each morning dose. In Group I patients, substantial plasma theophylline concentrations were seen only after the loading dose. Thereafter, the mean concentrations before or 2 h after the morning doese were always less than 4.0 µg/ml. Trough concentrations were usually below 2.0 µg/ml. In contrast patients in Group II achieved substantially higher plasma theophylline concentrations, with mean peak concentrations always 10 µg/ml or greater, and trough concentrations greater than 5 µg/ml on at least one occasion in every subject. The elimination half-lives after chronic administration in both groups were not significantly different from those obtained after single doses. Mean drug accumulation, measured as AUCss/AUC1, was 0.87±0.07 in Group I and 0.72±0.14 in Group II, indicating that accumulation had not occurred with either regimen. The mean increase in FEV1 2 h after the administration of a single dose was 19.2% after 375 mg and 16.7% after 250 mg. These results indicate that the recommended dosage regimen for microcrystalline theophylline preparation (375 mg stat and 125 mg 4 times daily) produces inadequate plasma theophylline concentrations: 250 mg 4 times daily would appear to be likely to result in satisfactory theophylline levels in more patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00606679
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  • 6
    Digitale Medien
    Digitale Medien
    Therapeutic traditions in Northern Ireland, Norway and Sweden: I. Diabetes (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 513-519 
    Details
    ISSN: 1432-1041
    Schlagwort(e): diabetes ; therapy ; antidiabetic drugs ; therapeutic traditions ; questionnaire survey ; drug utilization ; international differences
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A questionnaire survey was carried out to explore differences in the approach to treatment of patients with Type II diabetes between physicians in Northern Ireland, Norway and Sweden, and to discover to what extent it could account for the three-fold difference in drug use between the countries. A representative sample of 400 physicians in each country was asked to give their opinions on the choice of therapy for three model cases designed to cover the spectrum of treatment — from diet alone to insulin. Significantly more Swedish (65%) than Northern Irish (51%) and Norwegian (52%) doctors suggested diet alone for uncomplicated diabetes recently discovered in a middle aged, overweight man. For symptomatic diabetes in a 76 year old overweight woman with few retinal microaneurysms, the majority of physicians in all three countries suggested treatment with sulphonylureas. Biguanides were here a more common alternative in Northern Ireland than in Scandinavia. For suspected secondary treatment failure in a 63 year old woman with no signs of complications, insulin was suggested by 71% of the Norwegian doctors but only by 44 and 49% of those in Northern Ireland and Sweden, respectively. General practitioners tended to suggest oral treatment earlier and to maintain it longer than hospital physicians. The study has demonstrated significant differences in the approach to treatment of Type II diabetes mellitus between physicians in the three countries. However, the differences were more prominent in the choice of drugs than in the threshold of drug treatment. The results also fit with qualitative but not with quantitative differences in drug sales between the countries, suggesting that important differences may exist in the prevalence of clinically recognized Type II diabetes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542408
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  • 7
    Digitale Medien
    Digitale Medien
    β-Blockers and psychometric performance: Studies in normal volunteers (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 35-38 
    Details
    ISSN: 1432-1041
    Schlagwort(e): atenolol ; benzodiazepines ; nadolol ; propranolol ; psychomotor tests ; β-adrenoceptor antagonists ; lipophilicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Tests of psychometric function were performed in young, normal volunteers taking several β-adrenoceptor antagonists. With single doses of atenolol, a cardioselective hydrophilic β-blocker, dosedependent effects were apparent and were maximal at a dose of 200 mg. The lipophilic non-selective β-blocker, propranolol, also produced significant impairment of psychomotor tests but these were inversely related to dose, the longest effects being at a dose of 40 mg but with little effect at 320 mg. Subsequently, a multisubject comparison of propranolol and atenolol confirmed these findings and showed the effects to be of the same order of magnitude as those produced by diazepam. Chronic administration of atenolol 100 mg, nadolol 80 mg and diazepam 5 mg daily for seven days showed some effects with all drugs during the test period; however, these were sporadic rather than persistent. Overall, β-Blockers do appear to have central effects in man which can be demonstrated by psychomotor tests. However, the relevance of these central effects to maintenance therapy and skilled performance is unclear.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00543708
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  • 8
    Digitale Medien
    Digitale Medien
    Validation of observed differences in the utilization of antihypertensive and antidiabetic drugs in Northern Ireland, Norway and Sweden (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 1-8 
    Details
    ISSN: 1432-1041
    Schlagwort(e): antihypertensive drugs ; antidiabetic drugs ; prescribing practice ; utilization ; Northern Ireland ; Norway ; Sweden
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The amount of antihypertensive and antidiabetic drugs based of defined daily doses per 1000 inhabitants per day varies two to three fold between Northern Ireland, Norway, and Sweden. We explored whether variations based on the universally applied defined daily doses might be accounted for by national differences in the actual average prescribed daily doses. Use of prescribed daily doses for antihypertensive drugs resulted in Northern Irish and Norwegian consumption figures which were respectively 40 and 21% lower than the Swedish one, compared to 38 and 25% when defined daily doses were used. The effect of population age-sex differences on the gross defined daily doses per 1000 inhabitants per day figures was determined by applying the Northern Irish or Norwegian age-sex group proportions to Swedish age-sex specific sales data. Taking population differences into account would have resulted in antihypertensive drug use being 21 rather than 38% less in Northern Ireland and 18 rather than 25% less in Norway. Also adjustment for prescribed daily doses left an unexplained difference of 23% between Sweden and Northern Ireland and 14% between Sweden and Norway. For oral antidiabetics use of prescribed daily doses resulted in a Northern Irish — Swedish difference of 62% compared to 67% when defined daily doses were used. Simultaneous adjustment for population differences and prescribed to defined daily dose variations left a 52% difference.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00547360
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  • 9
    Digitale Medien
    Digitale Medien
    Pharmacokinetics, efficacy and adverse effects of sublingual salbutamol in Patients with asthma (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 567-571 
    Details
    ISSN: 1432-1041
    Schlagwort(e): salbutamol ; sublingual ; oral ; inhaled ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Administration of drugs by the sublingual route provides rapid systemic absorption and avoids first-pass metabolism. The purpose of the present study was to assess the pharmacokinetics, efficacy and adverse effects of standard salbutamol tablets given by this route to patients with asthma. Seven asthmatic patients were given either sublingual salbutamol tablet 2 mg (SL), swallowed tablet 2 mg (O), metered dose inhaler 200 µg (MDI) or placebo (PL), in a randomized single-blind cross-over design. Airways responses (FEV1, FVC, PEFR), finger tremor (Tr), heart rate (HR), plasma potassium (K) and plasma salbutamol were measured over a 6 h period following drug administration. There were highly significant changes in FEV1 with MDI, O and SL routes compared with PL, although the response to MDI was greater and more rapid than with O or SL. There were similar findings for FVC and PEFR responses. There were no adverse effects with MDI, whereas both 0 and SL produced significant tremor responses. There were no differences between O and SL for any of the pharmacodynamic parameters. In addition, pharmacokinetic profiles for O and SL were also similar apart from an initial delay in absorption with SL. There were however, no significant differences in any of the pharmacokinetic parameters, between O and SL. This suggests that buccal absorption of salbutamol was negligible, and that systemic absorption occurred after swallowing of the dissolved sublingual tablet. These results show that sublingual administration of salbutamol tablet has no clinical benefit over the oral route.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562546
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  • 10
    Digitale Medien
    Digitale Medien
    Evaluation of the metabolic responses to inhaled salbutamol in the measurement of beta2-adrenoceptor blockade (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 297-300 
    Details
    ISSN: 1432-1041
    Schlagwort(e): atenolol ; salbutamol ; beta-adrenoceptor antagonists ; cardioselectivity ; metabolic response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The aim of the present study was to evaluate whether metabolic responses to inhaled salbutamol may be used to measure the cardioselectivity of beta-adrenoceptor antagonists. We therefore studied the effects of oral doses of atenolol 50 mg, 100 mg, 200 mg (A50, A100, A200), propranolol 40 mg (P40), and placebo (Pl) on the hypokalaemic (K) and hyperglycaemic (Glu) responses to inhaled salbutamol in five healthy subjects. Increasing doses of atenolol were associated with a progressive attenuation of ΔK compared with placebo: −0.72 mmol·l−1 (Pl) vs −0.20 mmol·l−1 (A200). However, ΔK with A200 was significantly different from the response with P40: +0.12 mmol·l−1. There were partial reductions in the hyperglycaemic response with the beta-adrenoceptor antagonists, although this was only significant (compared with Pl) for P40: ΔGlu 1.92 mmol·l−1 (Pl) vs 0.76 mmol·l−1 (P40). These results show that beta2-adrenoceptor blockade by atenolol is a dose-dependent phenomenon, which may be measured by the attenuation of salbutamol-induced hypokalaemia. However, beta2-adrenoceptor blockade by atenolol 200 mg was less than that by propranolol 40 mg. The glucose response to salbutamol was only partially blocked by propranolol and may therefore not be suitable to assess beta2-adrenoceptor antagonism.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00679788
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