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  • 1
    Electronic Resource
    Electronic Resource
    Effects of angiotensin converting enzyme inhibitor, perindopril, on autonomic reflexes (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 177-182 
    Details
    ISSN: 1432-1041
    Keywords: perindopril ; blood pressure ; heart rate ; parasympathetic ; sympathetic ; converting enzyme inhibitor ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of the angiotensin converting enzyme inhibitor, perindopril, on autonomic function was assessed in a double blind, placebo controlled, crossover study in 10 normotensive males. Eight milligram of perindopril given orally lowered blood pressure without a change in heart rate. Perindopril enhanced the vagally mediated heart rate variation with deep breathing. There was no impairment of the responses to either bicycle exercise at 175 W for 5 min or isometric handgrip. The pressor response to cold was not changed and the response to the Valsalva manoeuvre was unaltered. These results suggest that the absence of tachycardia after perindopril may be in part related, as has been reported with other converting enzyme inhibitors, to enhanced cardiac parasympathetic tone. Vagomimetic action may be a property of converting enzyme inhibitors in general.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614298
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  • 2
    Electronic Resource
    Electronic Resource
    The haemodynamic and humoral effects of treatment for one month with the angiotensin converting enzyme inhibitor perindopril in salt replete hypertensive patients (1987)
    Springer
    European journal of clinical pharmacology 31 (1987), S. 519-524 
    Details
    ISSN: 1432-1041
    Keywords: perindopril ; hypertension ; angiotensin converting enzyme inhibition ; renin-angiotensin system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the effects of treatment for one month with perindopril, 4 or 8 mg once daily, in seven hypertensive patients. Blood pressure was lowered from 164/93 mm Hg to 145/84 mm Hg by 4 mg of perindopril and after one month remained at 142/82 mm Hg. Neither postural hypotension nor tachycardia occurred. Inhibition of plasma angiotensin converting enzyme (ACE) lasting for over 24 h was achieved and there was a significant increase in plasma renin activity (PRA). Maximum plasma concentrations of the active metabolite of perindopril, S-9780, were detected four h after oral administration. After treatment for one month there was evidence of reduced sensitivity of plasma ACE to the action of the inhibitor. The plasma concentration of S-9780 required to produce 50% inhibition of plasma ACE rose from 2.4 ng · ml−1 following the first dose to 5.5 ng · ml−1 after one month.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606623
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    The influence of beta-adrenoceptor antagonists with and without partial agonist activity on exercise tolerance and muscle lactate production (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 415-417 
    Details
    ISSN: 1432-1041
    Keywords: Epanolol ; metoprolol ; beta adrenoceptor antagonist ; exercise ; lactate ; intrinsic activity ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Epanolol is a beta-adrenoceptor antagonist with partial agonist activity, a property which could be useful in reducing the fatigue associated with beta blockers. In a double-blind, randomized, crossover study we have investigated the effects of metoprolol 100 mg b.d., epanolol 100 mg b.d., and epanolol 200 mg b.d. on blood pressure, heart rate, and exercise-induced fatigue in 10 hypertensive men. Fatigue was measured subjectively by the Borg rating scale and objectively by blood lactate concentrations. Resting and exercise heart rates were lower with metoprolol than with either dose of epanolol. Preexercise standing diastolic blood pressure was lowered by metoprolol, but there were no other treatment effects on blood pressure. Exercise-induced fatigue was not altered by any treatment, whether measured subjectively or objectively. These results do not support the hypothesis that partial agonist activity improves exercise tolerance in hypertensive patients treated with beta-adrenoceptor antagonists.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637640
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Efficacy and Tolerability of Lifarizine in Acute Ischemic Stroke. A Pilot Study (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 765 (1995), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1995.tb16599.x
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of a glycine site antagonist (gavestinel) following multiple dosing in patients with acute stroke (2000)
    Springer
    European journal of clinical pharmacology 55 (2000), S. 867-872 
    Details
    ISSN: 1432-1041
    Keywords: Key words Gavestinel ; Pharmacokinetics ; Acute stroke
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The objective of this study was to characterize the pharmacokinetics of gavestinel in patients with acute stroke. Methods: Gavestinel was administered as an 800-mg loading dose and followed by either 100-, 200-, or 400-mg maintenance doses given every 12 h for five doses. Blood and urine samples were collected for pharmacokinetic evaluation. The pharmacokinetics of gavestinel were determined using compartmental analysis. Results: The mean clearance (CL) and central (Vc) and steady-state (Vss) volumes of distribution across the dose groups were 0.31–0.40 l · h−1, 3.3–3.9 l, and 9.8–17 l, respectively. The mean terminal half-life ranged from 29 h to 56 h. Gavestinel was extensively bound to plasma protein (median percentage free 〈0.01). During gavestinel administration, some patients exhibited elevated levels of bilirubin, which may be the result of shared mechanisms of elimination (glucuronide conjugation and excretion in bile). Conclusions: This study characterized the pharmacokinetics of gavestinel following multiple doses in acute stroke patients and showed that the pharmacokinetics are similar for increasing maintenance doses. The high protein binding of gavestinel was confirmed in acute stroke patients. A pharmacokinetic interaction between gavestinel and bilirubin may contribute to the increase in bilirubin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050709
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    Paper (German National Licenses)
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  • 6
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of an ACE inhibitor, S-9780, in man: Evidence of tissue binding (1989)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 17 (1989), S. 529-550 
    Details
    ISSN: 1573-8744
    Keywords: nonlinear tissue binding ; angiotensin converting enzyme ; S-9780 ; perindopril
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Pharmacokinetic data from 20-min constant rate infusions of the ACE inhibitor S-9780 1 mg to 16 subjects were studied for evidence of nonlinearity. A hierarchy of standard compartmental models and of nonlinear binding models was fitted to the data by least squares nonlinear regression and the most appropriate model was chosen on the basis of F-ratio tests, Schwarz criteria, and residual plots. A one-compartment model which included saturable tissue and plasma binding components allowed the best overall description of the data. Median parameter estimates from this model suggest that approximately 308 nmol of plasma binding sites and 572 nmol of tissue binding sites were present and that the total plasma concentration of S-9780 at 50% saturation of binding sites was 16.5 nmol L−1. The elimination half-life for free drug in plasma was only 30 min. This model describes the discrepancy previously noted between accumulation and apparent elimination half-lives for long-acting ACE inhibitors and offers a noninvasive method for assessment of tissue-bound ACE inhibitorin vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01071348
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