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  • pharmacokinetics  (6)
  • Atenolol  (4)
  • metabolic response  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of sotalol during pregnancy (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 521-524 
    Details
    ISSN: 1432-1041
    Keywords: sotalol ; beta-adrenoceptor antagonist ; pregnancy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609896
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  • 2
    Electronic Resource
    Electronic Resource
    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
    Keywords: Microcrystalline theophylline ; chronic obstructive airways disease ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606679
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of propranolol during pregnancy (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 583-587 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; pregnancy ; beta-adrenoceptor antagonist ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00556896
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of combined atenolol and nifedipine administration on psychomotor performance in normal subjects (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 229-233 
    Details
    ISSN: 1432-1041
    Keywords: Atenolol ; Nifedipine ; psychomotor performance ; diazepam ; combination therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The aim of the present study was to evaluate the central effects of single doses of the β-adrenoceptor antagonist atenolol and the calcium antagonist nifedipine retard, alone and in combination, in normal subjects. Twelve normal males received single oral doses of atenolol 100 mg, nifedipine retard 20 mg, atenolol 100 mg and nifedipine retard 20 mg in combination, diazepam 5 mg (active control), and each of two matching placebos in a double-blind, randomised fashion. Psychomotor performance was assessed using digit symbol substitution, letter cancellation (LCT), continuous attention, choice reaction time, finger tapping, immediate recall and short-term memory. Two flash fusion and critical flicker fusion thresholds were measured and subjective assessments made using visual analogue scales (VAS). Diazepam 5 mg significantly worsened LCT scores at 4h, significantly impaired alertness at 2 h and 4 h, and tended to increase reaction time and impair continuous attention and physiological measurements. Atenolol 100 mg alone significantly reduced alertness at 2 h and 4 h, and also tended to impair physiological measurements. Nifedipine retard 20 mg produced no significant psychomotor effects. Combined atenolol and nifedipine retard administration produced a small but significant improvement in continuous attention and a reduction in body sway, with no adverse effects being evident on performance or subjective awareness. The results suggest that no significant adverse effects on psychomotor performance are produced by single doses of atenolol 100 mg and nifedipine retard 20 mg when given together in normal subjects. The combination may therefore be useful in the treatment of hypertensive patients requiring dual therapy, and in whom adverse central effects are of particular importance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00198303
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  • 5
    Electronic Resource
    Electronic Resource
    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
    Keywords: Sotalol ; β-adrenoceptor blocking drugs ; exercise tachycardia ; efficacy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606550
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  • 6
    Electronic Resource
    Electronic Resource
    Central effects of combined bendrofluazide and atenolol administration (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 539-543 
    Details
    ISSN: 1432-1041
    Keywords: Atenolol ; Bendrofluazide ; Psychomotor performance ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twelve normal male subjects received single oral doses of atenolol 100 mg (AT), bendrofluazide 5 mg (BFZ), combined atenolol 100 mg and bendrofluazide 5 mg (AT/BFZ), diazepam 5 mg (Dz), or one of two matching placebos, on each of 6 study days. Tests of psychomotor performance [digit symbol substitution (DSST), letter cancellation (LCT), continuous attention, choice reaction time (CRT), finger tapping, short-term memory, body sway], physiological measurements [critical flicker fusion (CFF), two-flash fusion (2FF)] and subjective assessments using visual analogue scales (VAS), were performed at 2 and 4 hours post-ingestion. Dz (active control) significantly worsened VAS scores at 2 h (+0.68) and reduced DSST scores at both 2 h (−15.0) and 4 h (−11.0). AT and BFZ given alone, each produced significant worsening of VAS at 2 h [AT +1.0; BFZ +1.38], but had no significant effects on performance. In combination however, AT/BFZ at 4 h produced significant impairment of DSST scores (−10.4), reduced finger tapping (−16.5) and increased involuntary rest pauses (+16.5). Despite these effects, no change in VAS scores occurred. In summary, we have demonstrated significant impairment of psychomotor performance in normal subjects with the AT/BFZ combination, which was not evident with the single agents and which occurred in the absence of a change in subjective awareness. These central effects may have important clinical implications for patients taking combined antihypertensive medication.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315311
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  • 7
    Electronic Resource
    Electronic Resource
    Central effects of repeated administration of atenolol and captopril in healthy volunteers (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 23-28 
    Details
    ISSN: 1432-1041
    Keywords: Atenolol ; Captopril ; Central effects ; short term administration ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The central effects of atenolol (50 mg tds) and captopril (50 mg tds) ingested for a period of seven days were studied in ten healthy volunteers. A placebo and two active control drugs, methyldopa (250 mg tds) and oxazepam (10 mg), were included in the design. Oxazepam was ingested on the seventh day only, with a placebo being taken on the preceding six days. On the seventh day, central effects of the drugs were tested at 10.00–11.00 h (session 1), immediately before the subjects' last dose of each drug and at 2.5–3.5 h after the final dose of each drug (1330–1430 h, session 2). Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, critical flicker fusion and two flash fusion. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. Recordings of the EEG and body sway were carried out. Neither atenolol nor captopril altered performance at any of the skills tested. There were no effects on subjectively assessed alertness or mood with captopril, while atenolol significantly increased wakefulness in session 2 and when the two sessions were meaned. Similarly, captopril did not modify body sway, while with atenolol there was a significant decrease in activity in the frequency range 1.0–2.75 Hz from session 1 to session 2. Both captopril and atenolol modified the electrical activity of the brain, with captopril increasing delta and theta activity and atenolol reducing delta, alpha and beta activity. Methyldopa significantly increased the number of involuntary rest pauses in the finger tapping task, and the choice reaction time from session 1 to session 2. There was a decrease in passivity during the first session and an increase in wakefulness in session 2 with methyldopa. This drug also decreased body sway in the frequency range 1.0–2.75 Hz activity in session 2, while oxazepam decreased bodys was at 1.0 to 2.75 Hz and increased activity at 2.5–3.0 Hz in session 2. Oxazepam reduced delta, theta and alpha content of the EEG. The present study has been unable to demonstrate any development of adverse central effects with captopril over a period of 7 days of drug ingestion. With atenolol adverse effects were present following short term dosing but were not more pronounced than with acute ingestion seen in previous studies. However effects on the electrical activity of the brain with atenolol remained after 7 days suggesting that the changes reported previously with single ingestions do not disappear.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195911
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  • 8
    Electronic Resource
    Electronic Resource
    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
    Keywords: salbutamol ; sublingual ; oral ; inhaled ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562546
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  • 9
    Electronic Resource
    Electronic Resource
    Beta-adrenoceptor responses to inhaled salbutamol in normal subjects (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 239-245 
    Details
    ISSN: 1432-1041
    Keywords: beta-adrenoceptor ; salbutamol ; airways response ; tremor ; haemodynamic response ; metabolic response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The aim of the present study was to quantify and compare the airways and systemic beta-adrenoceptor responses to inhaled salbutamol in normal subjects. Seven non-atopic, normal subjects were given cumulative doubling doses of inhaled salbutamol (100 µg to 4000 µg) or placebo in a single-blind cross-over design. Airways (sGaw, FEF 50%, FEF 25%), tremor, haemodynamic and metabolic responses were measured at each dose increment. There were dose-related changes in sGaw, FEF 50% and FEF 25% up to a plateau at 1.0 mg. Analysis of individual responses showed that most subjects required either 1.0 or 2.0 mg for maximum bronchodilatation, independent of the parameter of airflow. There was no correlation between maximum response and baseline airway calibre. In contrast to airways effects, systemic beta-adrenoceptor responses did not occur until 500 µg, and a ceiling in the dose-response curve was not reached. Therer were significant correlations between air-ways, tremor and haemodynamic responses, and between different metabolic variables. The intraindividual variability was greatest for tremor and sGaw, although this was small in comparison to the size of maximum change with salbutamol. The converse applied to the hypomagnesaemic response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558154
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  • 10
    Electronic Resource
    Electronic Resource
    Single dose and steady-state pharmacokinetics of 4 mg and 8 mg oral salbutamol controlled-release in patients with bronchial asthma (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 49-52 
    Details
    ISSN: 1432-1041
    Keywords: salbutamol ; asthma ; controlled-release formulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifteen patients with asthma were given salbutamol controlled-release (SCR) 4 mg or 8 mg twice daily for seven days, in a randomised double-blind cross-over design. Plasma salbutamol levels were measured after the first and fifteenth doses for a 12 h period following drug ingestion. At steady-state the geometric mean values for Cmax were 8.2 ng/ml for 4 mg, and 16.1 ng/ml for 8 mg. Median tmax values were 300 and 240 min respectively. The geometric mean AUC (0–12) were 4507 ng·min·ml−1 and 8980 ng·min/ml. Peak to trough fluctuation ratios were 0.577 and 0.572. There were no significant differences between 4 mg or 8 mg formulations, for any of the parameters measured, after appropriate corrections for dose. The concentration-time profiles at steady-state showed little fluctuation in plasma salbutamol levels over the twelve hour dosing interval. These results show that 4 mg and 8 mg formulations of SCR provide smooth plasma profiles at steady-state with a twice daily dosing regime.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609424
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