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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 21 (1982), S. 287-291 
    ISSN: 1432-1041
    Keywords: tolmesoxide ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tolmesoxide is a new, direct-acting vasodilator drug for use in the management of both hypertension and cardiac failure. In 6 essential hypertensives inadequately controlled by combined β-blocker and diuretic therapy (average supine blood pressure 178/103 mm Hg) the addition of tolmesoxide (300–900 mg daily) was associated with a significant improvement in blood pressure control (average supine blood pressure 161/89 mmHg). The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide have also been studied because, particularly at higher doses, the drug has been associated with upper gastrointestinal upset and it has been empirically recommended that it be taken with food. The blood pressure and heart rate responses were not significantly different when tolmesoxide was taken fasting or with food. Food resulted in a significant reduction in the peak plasma tolmesoxide concentration (2.14 µg/ml compared to 2.97 µg/ml) and a significant increase in the time to reach peak plasma concentration (1.67 h compared to 0.63 h). Although there was no impairment of its hypotensive effect, food significantly altered the pharmacokinetics of tolmesoxide and may therefore be useful in reducing the gastrointestinal disturbance associated with its use. In the treatment of inadequately controlled hypertension, tolmesoxide has a limited role as an alternative vasodilator.
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 345-347 
    ISSN: 1432-1041
    Keywords: disopyramide ; myocardial infarction ; oral bioavailability ; changing pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In the acute phase of myocardial infarction it is recognized that serum disopyramide concentrations may be lower than expected. This has generally been attributed to reduced oral bioavailability. This report describes data obtained routinely from 6 patients with acute myocardial infarction and cardiac dysrhythmias treated initially with intravenous disopyramide. Serum disopyramide concentrations were consistently lower than expected, on average by 2.6 µg/ml. This was interpreted as being due to relatively high drug clearance, calculated as 6.7±1.5 l/h, compared to expected values of 3–4 l/h. Dosage schedules determined on the basis of the acute phase pharmacokinetics subsequently produced higher than predicted concentrations at later times on average by 2.8 µg/ml. Clearance at this time was calculated to be 3.1±0.6 l/h. Thus even with intravenous disopyramide therapy there are problems with changing pharmacokinetic parameters after myocardial infarction.
    Type of Medium: Electronic Resource
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 45 (1993), S. 425-430 
    ISSN: 1432-1041
    Keywords: Amlodipine ; Felodipine ER ; pharmacokinetics ; blood pressure response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This study investigated potential therapeutic differences between Amlodipine 5 mg and Felodipine ER 10 mg in 12 normotensive/borderline hypertensive subjects by comparison of the plasma drug concentration-time profiles and the blood pressure and heart rate responses. There was significantly less trough-to-peak variability in plasma drug concentrations with amlodipine with a ratio of 67%, compared to 37% for felodipine. Correspondingly there was less variability with amlodipine in the blood pressure reductions across the dosage interval. Overall, amlodipine displayed a more consistent hypotensive effect across 24 hours and lower blood pressure values at trough, i. e. 24 hours post-dose.
    Type of Medium: Electronic Resource
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 21 (1981), S. 97-102 
    ISSN: 1432-1041
    Keywords: mianserin ; clonidine ; pharmacodynamics ; interaction ; alpha2-receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary There is evidence that clonidine's hypotensive effect is reduced by the concurrent administration of tricyclic antidepressants. It has been proposed that this results from an interaction at α2-receptors in the brain stem where clonidine acts as a relatively selective agonist and the tricyclic antidepressants as antagonists. Mianserin is an antidepressant with a tetracyclic structure and, although it has been reported to cause less cardiovascular disturbance, there is evidence that it also has α-adrenoceptor blocking effects. This study in 6 normotensive healthy male volunteers was designed to investigate a possible interaction between clonidine and the antidepressant mianserin. Administration of the first dose of 20 mg mianserin was associated with acute cardiovascular effects, notably transient postural hypotension, but no significant disturbance of heart rate or blood pressure was detected after 3 days continuous treatment with mianserin 20 mg tid. Following pre-treatment with mianserin or placebo the responses to a single oral dose of 300 µg clonidine were then assessed. The combination of mianserin and clonidine was not associated with any attenuation of clonidine's hypotensive effect, erect or supine, but there was significant attenuation of clonidine's supine bradycardic effect. There was no evidence that mianserin interfered with the ability of clonidine to diminish salivary flow, cause sedation, and reduce catecholamine output, but it was noted that mianserin itself had a very pronounced sedative effect. Mianserin alone had no significant effect on salivary flow. This short term study demonstrates that mianserin does not significantly interfere with the responses to a single oral dose of clonidine.
    Type of Medium: Electronic Resource
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