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  • 1
    ISSN: 1432-1041
    Keywords: Chlorthalidone ; diuretics ; drug plasma concentration ; protein binding ; red blood-cell concentration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A gas chromatographic method has been employed to determine chlorthalidone in plasma and whole blood after therapeutic doses. Radioactively labelled chlorthalidone was used for in vitro studies of the uptake of chlorthalidone from plasma by red blood cells. Chlorthalidone was markedly concentrated in red cells and as a compartment they would account for at least 30% of total drug in the body after multiple doses. The ratio between the plasma and red cell concentration of chlorthalidone varied between individuals. After a single oral dose of 50 mg in 6 healthy volunteers chlorthalidone was eliminated with a half-life of 51 to 89 hours. The apparent volume of distribution varied between 3 and 13 1/kg and the clearance between 53 and 145 ml/min. The mean steady-state plasma concentrations during treatment with a standard dose of 50 mg daily (n=10) varied 5-fold between individuals. During the steady state approximately 50% of the daily dose was excreted unchanged in the urine during 24 hrs. The plasma levels observed in patients were higher than those predicted from the single oral dose studies in healthy volunteers.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Drug hydroxylation ; drug interaction ; drug plasma levels ; nortriptyline ; 10-hydroxynor-triptyline ; perphenazine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of nortriptyline and perphenazine were measured in six patients on continuous nortriptyline treatment before, during and after oral administration of perphenazine 4 mg t.i.d. In four patients the plasma levels of the conjugated and unconjugated principal metabolite 10-hydroxy-nortriptyline were also measured. Urinary excretion of conjugated and unconjugated 10-hydroxy-nortriptyline and plasma levels of perphenazine were determined in all six patients. During treatment with perphenazine two patients showed a slight increase in the plasma level of nortriptyline. The changes in metabolite excretion rate were inconclusive. Thus, there did not appear to be any important pharmacokinetic interaction between the two drugs at the doses used, which were normal therapeutic doses. The previously reported inhibitory effect of perphenazine on the metabolism of nortriptyline probably depended therefore, either on administration of a higher dose of perphenazine, or on treatment in the reverse sequence — a single dose of nortriptyline was given to patients already receiving perphenazine.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1986), S. 415-418 
    ISSN: 1432-1041
    Keywords: pindolol ; age effect ; pharmacokineticsrenal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and beta-blocking effect of pindolol has been compared in 20 patients with essential hypertension (WHO Stage I), 10 below 25 years of age and 10 older than 60 years. Each patient received pindolol 10 mg p.o. once a day for 5 days. The area under the curve (AUC) of pindolol was larger in the old than in the young patients both on the first (p〈0.05) and the fifth (p〈0.01) days. The AUC of pindolol was 14% higher on the fifth day compared to the first day in the elderly group, indicating minor accumulation at steady-state. There was no change in AUC in the young patients. Endogenous creatinine clearance was lower in the old (80±9 ml/min) than in the young patients (150±45 ml/min). The beta-blocking effect did not differ between the groups at 2h after administration of pindolol on Days 1 or 5. However, 24 h after the first and fifth doses approximately 60% of the beta-blockade persisted in the old group whereas 17 and 19% of the beta-blockade, respectively, persisted in the young group; the difference between the groups was statistically significant (p〈0.01). The most probable explanation for the more sustained beta-blocking effect in the elderly is the physiologically decrease in renal function, which results in a more sustained plasma level of pindolol in those patients.
    Type of Medium: Electronic Resource
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