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  • 1
    Electronic Resource
    Electronic Resource
    A pharmacokinetic study of the active metabolite of nabumetone in young healthy subjects and older arthritis patients (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 299-305 
    Details
    ISSN: 1432-1041
    Keywords: nabumetone ; rheumatoid arthritis ; pharmacokinetics ; old patients ; NSAID
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have performed a detailed pharmacokinetic study of the plasma concentrations of the major active metabolite of nabumetone, 6-methoxy-2-naphthylacetic acid (6 MNA), attained after a single dose and during chronic administration comparing the results of a group of young healthy volunteers with those of a group of elderly arthritic patients. The latter had higher peak plasma concentrations of 6MNA and slower rates of elimination but there is no tendency for the drug to accumulate unpredictably in the old. Disease activity also influences plasma concentration, those with more active disease, and lower serum albumin concentrations had lower AUC values.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558163
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  • 2
    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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  • 3
    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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  • 4
    Electronic Resource
    Electronic Resource
    Inter- and intra-subject variability of nitrendipine and the effects of food (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 357-360 
    Details
    ISSN: 1432-1041
    Keywords: nitrendipine ; food intake ; pharmacokinetics ; variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of nitrendipine were measured, after single (20 mg) oral doses, in young healthy volunteers. On three occasions the subjects ingested the dose having fasted overnight. Data from these three occasions were used to assess variability in nitrendipine pharmacokinetics and both inter- and intra-subject variability were high. On a fourth occasion, the subjects took the tablet after a standard meal. The effects of food on nitrendipine pharmacokinetics, based on the comparison of data from the first fasting visit and the food visit, were negligible.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543969
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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 pharmacokinetics of diclofenac sodium in patients with active rheumatoid disease (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 331-334 
    Details
    ISSN: 1432-1041
    Keywords: diclofenac sodium ; rheumatoid disease ; healthy subjects ; serum albumin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic data for diclofenac sodium has been well established in healthy volunteers, whereas in patients with rheumatoid arthritis very little information is available in the literature. A single oral dose of enteric-coated diclofenac sodium was given to 10 patients with active rheumatoid disease, adopting the same procedures used for a group of 10 healthy volunteers in whom pharmacokinetic data was already available. Plasma specimens were collected over a period of 8h following administration and concentrations of diclofenac determined by GLC. Resulting plasma concentration curves were similar to those obtained in the healthy subjects in that areas under curves and terminal half-lives were comparable. However, peak concentrations of diclofenac were significantly reduced in the rheumatoid patients. The lower peak concentrations were correlated with the lower serum albumin levels in the patients which are associated with active rheumatoid disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637622
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  • 7
    Electronic Resource
    Electronic Resource
    Variability of beta-blocker pharmacokinetics in young volunteers (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 37-42 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; propranolol ; oxprenolol ; pharmacokinetics ; acetubolol ; diacetolol ; oral contraceptive
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of metoprolol, propranolol oxprenolol, acebutolol and its metabolite diacetolol were measured after single oral doses in young healthy volunteers. In order to assess the inter-and intra-subject variability the following pharmacokinetic parameters were compared: AUC o 24 , Cmax, tmax and t1/2. The smallest variation in inter-subject variability was seen with oxprenolol and acebutolol: intrasubject variability was more uniform. Female volunteers taking an oral contraceptive generally had higher AUC o 24 and Cmax values than those not. This finding reached statistical significance only for metoprolol AUC o 24 .
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061375
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  • 8
    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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  • 9
    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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  • 10
    Electronic Resource
    Electronic Resource
    Pharmacokinetic interactions between felodipine and metoprolol (1987)
    Springer
    European journal of clinical pharmacology 31 (1987), S. 575-578 
    Details
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This double-blind, cross-over study in healthy male subjects evaluated the pharmacokinetics of felodipine and metoprolol given both separately and in combination. During three, five-day study periods, felodipine 10 mg b.d., metoprolol 100 mg b.d. and a combination of the two, were given in random order. There was at least a 7-day washout period between each pharmacokinetic study day. Plasma levels of unchanged felodipine and metoprolol were measured for 24 h after the last dose, on the 5th day of each treatment period. Eight subjects, aged 19–22 years, completed the study. Both felodipine and metoprolol, given alone and in combination, were well tolerated. None of the felodipine pharmacokinetic variables (tmax, Cmax, Cmin, AUC (0–12) and t1/2) changed significantly when felodipine and metoprolol were given in combination. Cmax and AUC (0–12) for metoprolol increased significantly when metoprolol and felodipine were combined, although tmax, Cmin and t1/2 for metoprolol remained unchanged. The changes in metoprolol pharmacokinetics induced by felodipine are small and unlikely to be clinically important.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606633
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