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  • 1
    Electronic Resource
    Electronic Resource
    Separate and combined effects of nadolol and nifedipine on the cardiac response to exercise (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 113-117 
    Details
    ISSN: 1432-1041
    Keywords: nadolol ; nifedipine ; tachycardia ; cardiovascular response ; healthy volunteers ; pharmacokinetics ; exercise heart rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a placebo controlled exercise protocol using healthy volunteers the effects of nadolol 80 mg and 160 mg orally and of nadolol 80 mg during treatment with nifedipine 20 mg 8 hourly were compared. Resting systolic and diastolic blood pressures were reduced by both nifedipine (p〈0.05) and nadolol (p〈0.01) acting alone. An unexpected finding was that nifedipine alone significantly inhibited exercise tachycardia (p〈0.01) (8 to 12 h post dose). Predictably both doses of nadolol produced significant reduction in exercise tachycardia which was still apparent at 24 h. There was a linear relationship between log10 plasma nadolol concentration and reduction in exercise heart rate. The combined inhibitory effects of nifedipine and nadolol 80 mg on exercise heart rate showed partial additivity but did not summate. There was no pharmacokinetic interaction between the 2 drugs. The inhibition of exercise tachycardia by nifedipine, not previously documented, is consistent with an effect of the drug on the sinus node, as has been reported in in-vitro studies, and may contribute to the drugs efficacy in angina.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609676
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  • 2
    Electronic Resource
    Electronic Resource
    Exercise responses of healthy subjects in the evaluation of cardioselectivity ofβ-blockers (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 229-233 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; metoprolol ; acebutolol ; exercise testing ; healthy subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of intravenous propranolol, metoprolol, acebutolol and placebo on exercise-induced changes in heart rate and peak flow rate (PFR) have been studied in a group of healthy subjects. The three β-blockers produced significant and comparable reductions in exercise-induced tachycardia and the magnitude of the reduction was related to the log plasma concentration of each drug. Significant cardiac β-blockade was detectable for three hours after giving propranolol and for four hours after metoprolol and acebutolol. The exercise-induced changes in PFR were small and variable and were not significantly affected by any of the drugs. We conclude that, contrary to published reports, exercise-induced changes in heart rate and PFR in healthy subjects do not provide a satisfactory test system for assessing the selectivity of β-blockers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00618510
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  • 3
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of diclofenac sodium following intravenous and oral administration (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 405-410 
    Details
    ISSN: 1432-1041
    Keywords: diclofenac ; plasma levels ; intravenous bolus administration ; oral administration ; enteric coating ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of diclofenac were examined following single rapid intravenous injection and also following single oral doses to healthy female volunteers. After intravenous injection plasma levels of diclofenac fell rapidly and were below the limits of detection at 5.5 h postdosing. Individual drug profiles were described by a triexponential function and mean half-lives of the three exponential phases were 0.05, 0.26 and 1.1 h. After oral doses of enteric-coated tablets, the lag time between dosing and the appearance of drug in plasma varied between 1.0 and 4.5 h. However once drug absorption had commenced similar plasma drug profiles were obtained in different individuals. Peak plasma diclofenac levels ranged from 1.4 to 3.0 µg · ml−1. The mean terminal drug half-life in plasma was 1.8 h after oral doses. This value was not significantly greater than the value of 1.1 h following intravenous doses. Fifty percent of orally dosed diclofenac did not reach the systemic circulation due, predominantly, to first-pass metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00568201
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  • 4
    Electronic Resource
    Electronic Resource
    A single and multiple dose pharmacokinetic and pharmacodynamic comparison of conventional and slow-release metoprolol (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 87-92 
    Details
    ISSN: 1432-1041
    Keywords: beta-blocker ; metoprolol ; slow-release formulation ; multiple dosing ; blood pressure ; heart rate ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic and pharmacodynamic profiles for metoprolol have been measured in six healthy volunteers after single and multiple dosing with 100 mg conventional formulation twice daily and 200 mg slow-release formulation once daily. Both multidose regimes produced measurable predosing plasma concentrations of metoprolol. The plasma concentrations on the eighth day were greater than predicted by the single-dose data as indicated by the comparison of the total areas under the curve for the single dose and the dosage interval areas during multiple dosing. This increase may be associated with a change in the bioavailability and/or clearance of the drug and is currently being investigated. The peak concentrations for the two regimens were comparable but the times to peak with the slow-release regimen were significantly delayed. Both regimes produced significant beta-blocking effects over 24 h during multiple dosing, the reductions in exercise heart rate at 0 and 24 h on the eighth day corresponding to more than 20% of the maximum effect. Resting pulse rates and blood pressures were affected to a similar extent by the two regimens but neither significantly altered respiratory peak flow rates. The effects during multiple dosing were generally greater than those after a single dose and appeared to follow a more consistent trend. This observation, together with those for the plasma level data on the eighth day, illustrate the importance of performing multiple-dose studies in assessing beta-blocking drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562615
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  • 5
    Electronic Resource
    Electronic Resource
    The influence of food on the absorption of diclofenac after single and multiple oral doses (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 33-37 
    Details
    ISSN: 1432-1041
    Keywords: diclofenac sodium ; enteric-coating ; food ; absorption ; plasma levels ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single dose of enteric-coated diclofenac sodium was taken fasting and immediately after a standard breakfast by twelve healthy volunteers. A considerable delay in the onset of absorption was observed, non-fasting, varying from 2.5 to 12 h compared with 1.5 to 2.75 h when fasting. Peak plasma concentrations were reduced after food but areas under plasma concentration-time curves were comparable. Six subjects then took part in a study involving single and repeated dosing under fasting and non-fasting conditions. As before, prolonged and variable delays were observed when the enteric-coated tablets were taken after food. On repeated dosing, maximum plasma concentrations were reached after 6 h non-fasting compared with 2.5 h fasting. Peak plasma levels were, however, similar.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558380
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  • 6
    Electronic Resource
    Electronic Resource
    The influence of food on the absorption of diclofenac as determined by the urinary excretion of the unchanged drug and its major metabolites during chronic administration (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 39-44 
    Details
    ISSN: 1432-1041
    Keywords: diclofenac ; metabolites ; urinary excretion ; food ; absorption ; chronic administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six healthy subjects took diclofenac as an enteric-coated preparation twice daily for 17 days under the following conditions: (i) fasting, (ii) 15 min before a meal, and (iii) immediately after a meal. Urine specimens were collected on two separate days of each regimen and diclofenac and its total monohydroxylated metabolites measured. Statistical analysis of the excretion of diclofenac and its metabolites showed that, during chronic administration, absorption was not significantly influenced by dosing before or after food. The absorption pattern after both these modes of administration was comparable to that obtained under fasting conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558382
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of pirprofen in young volunteers and elderly patients (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 73-77 
    Details
    ISSN: 1432-1041
    Keywords: pirprofen ; arthritic disease ; pharmacokinetics ; elderly patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of pirprofen were measured in 11 elderly arthritic patients and 6 healthy young volunteers at the beginning and end of 8 days treatment with 400 mg doses twice daily. The mean ages of the two groups were 74.5 and 21.8 years, respectively. There were no statistically significant differences in peak concentrations, times to peak, areas under the curve or terminal elimination half-lives between the groups after single dosing. Repeated dosing increased plasma drug concentrations in both groups but the extent was as predicted from the single dose data. Again there were no statistically significant differences between the groups, although pre-dosing plasma concentrations were higher in the elderly compared with the young individuals. The results of this relatively small study suggest that advancing age and arthritic disease appear to have little influence on the pharmacokinetics of pirprofen and no modification in the dosage recommendation in elderly patients without overt renal or hepatic impairment is indicated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547372
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  • 8
    Electronic Resource
    Electronic Resource
    Introduction (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. S1 
    Details
    ISSN: 1432-1041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00578404
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  • 9
    Electronic Resource
    Electronic Resource
    Nadolol in combination with indapamide and xipamide in resistant hypertensives (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 29-33 
    Details
    ISSN: 1432-1041
    Keywords: nadolol ; indapamide ; xipamide ; resistant hypertension ; compliance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-four hypertensive patients have been studied. All had blood pressure recordings greater than 160/95 mmHg on 3 occasions whilst taking a beta blocker and two other antihypertensive agents in therapeutic doses. Compliance was checked by intermittent urine analysis for the relevant beta-blocker. These difficult to control hypertensives were treated with nadolol alone, nadolol plus indapamide and nadolol plus xipamide each for 2 months in random order. The aim was to reduce the blood pressure to below 160/95 mmHg. The supine blood pressure on nadolol alone (167/100 mmHg) was comparable to that on the previous three drug regimens (157/100 mmHg), the other two treatments were more effective (145/90 and 148/93 mmHg respectively). Hypokalaemia (serum potassium below 3.5 mmol/l) occurred in six individuals but occurred more frequently on xipamide than on indapamide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00635704
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  • 10
    Electronic Resource
    Electronic Resource
    Plasma levels and negative chronotropic effect of metoprolol following single doses of a conventional and sustained-release formulation (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 97-103 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; tachycardia ; healthy subjects ; conventional tablets ; slow release tablets ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels and associated reduction in exercise-induced tachycardia have been examined following the administration of single doses of metoprolol in conventional and slow-release tablets at different times to six healthy male subjects. The study was carried out in two parts. Initially, the tablets were given at 9 a. m. and the subjects were studied up to 14 h and then at 24 h. Subsequently, the same doses were given at 9 p. m. and the subjects were studied 12–24 h after drug administration (i. e. 9 a. m.–9 p. m. the next day). After giving the slow-release tablets the peak plasma levels were significantly lower but the drug persisted in the plasma at higher levels than after the conventional tablet. However, the beta-blocking effect was comparable from the two dosages. The results obtained for the period 12–24 h after the evening dose differed from the corresponding values after morning administration in that the plasma levels were higher and the betablocking effects more marked. Furthermore, the half-life values calculated from these data were significantly longer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609871
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