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  • protein binding  (2)
  • alpha2-receptors  (1)
  • changing pharmacokinetics  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 15 (1979), S. 69-71 
    ISSN: 1432-1041
    Keywords: phenytoin ; dialysis encephalopathy ; protein binding ; continuous ultrafiltration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Protein binding of phenytoin was assessed in one patient with dialysis encephalopathy before and after haemodialysis. Phenytoin concentrations were measured by radioimmunoassay and continuous ultrafiltration was used to assess phenytoin binding. At a serum concentration of 60 µmol.1−1 the percentage of phenytoin bound to serum albumin was considerably lower in the patient serum (79.95% predialysis; 92.09% postdialysis) than that in three normal sera (97.90±0.17%). Analysis of Scatchard plots indicated two classes of binding sites. In class I both the affinity and capacity for binding phenytoin were reduced in the pre and post-dialysis serum, whereas in class II the capacity of the uraemic serum was increased although the intrinsic association constant was greatly reduced. It was concluded that in vivo haemodialysis is associated with large fluctuations in the protein binding of phenytoin, in which the concentration of endogenous dialysible metabolites are strongly implicated.
    Type of Medium: Electronic Resource
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  • 2
    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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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 21 (1982), S. 311-313 
    ISSN: 1432-1041
    Keywords: piretanide ; uraemia ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The protein binding of piretanide was assessed by continuous ultrafiltration of sera from six normal subjects and seven uraemic subjects (samples taken immediately pre-dialysis). Throughout the range of piretanide concentrations studied (0.5–4.5 mM), the mean protein binding for uraemic serum was less than that for normal serum. This difference was significant (p〈0.05) at piretanide concentrations of 1.5 mM and above, but not at 1 mM where mean protein binding for uraemic serum was 88.1% compared to 94.2% for normal serum. Analysis of piretanide protein binding characteristics using the Rosenthal plot showed no significant differences between uraemic and normal serum with respect to primary or secondary binding sites. Parallel assessment by the Scatchard method suggests, as expected, that albumin is the principal protein moiety responsible for binding piretanide.
    Type of Medium: Electronic Resource
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  • 4
    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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