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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 7 (1974), S. 353-356 
    ISSN: 1432-1041
    Keywords: Alprenolol ; beta-blockade ; steady-state plasma concentration ; interindividual variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of alprenolol during one inter-dose interval and steady-state plasma concentrations have been determined in 30 patients treated for a prolonged period. The latter varied 25-fold between patients who received identical doses. Peak plasma concentrations were achieved at similar times in different patients, but only the level 5–7 h after administration was well correlated (r=0.997) with the steady-state concentration. The type of pharmacokinetic analysis described here is recommended for studies of the relationships between plasma concentration and effects of drugs with short half-lives.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 7 (1974), S. 455-459 
    ISSN: 1432-1041
    Keywords: Lidocaine ; phenytoin ; procainamide ; plasma concentration ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of phenytoin and procainamide on plasma concentrations of lidocaine have been studied in patients and dogs receiving continuous intravenous infusions of the latter drug. All drugs were given in doses that produced therapeutic plasma concentrations. In the patients, no changes were observed in plasma lidocaine levels after intravenous or intramuscular phenytoin, or after intravenous or oral procainamide. Similarly, in the dogs, intravenous phenytoin had no effect on plasma lidocaine concentrations. However, in both patients and dogs a high incidence of CNS side-effects was recorded during lidocaine — phenytoin combination therapy, which suggests a potential pharmacodynamic interaction between them. The absorption of phenytoin administered intra-muscularly was impaired, probably because of pH-dependent crystallization. This route of administration should be avoided in acute treatment with phenytoin.
    Type of Medium: Electronic Resource
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  • 3
    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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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 8 (1975), S. 91-96 
    ISSN: 1432-1041
    Keywords: Carbamazepine ; pharmacokinetics ; man ; diphenylhydantoin ; phenobarbital ; plasma binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Carbamazepine (2.7–3 mg/kg) was administered orally as an alcoholic solution (50% v/v) to eight healthy volunteers. Two of the subjects were also given 50 mg and 100 mg of carbamazepine in alcoholic solution and 200 mg as a tablet. Plasma concentrations, which were analysed by mass fragmentography, reached a maximum 1 – 7 hours after dosing, and then declined monoexponentially with half-lives ranging from 24 to 46 hours. The half-lives were independent of dose. The apparent distribution volume ranged from 0.79 to 1.40 l/kg. It was found that 72% of carbamazepine was bound to plasma proteins with little interindividual variation, and this was not influenced by the presence of diphenylhydantoin or phenobarbital in therapeutic concentrations. The pharmacokinetic parameters calculated from single oral doses were used to predict the steady-state plasma concentration expected after treatment with multiple doses of 200 mg three times daily. The predicted steady-state concentration was 2 – 3 times higher than that reported in patients undergoing chronic treatment with carbamazepine at this dose level, i.e. the pharmacokinetics of carbamazepine apparently change during multiple dosing.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: α-methyldopa ; plasma concentration ; hypertension ; sulphate conjugation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations of free α-methyldopa and methyldopa sulphate conjugate were measured in 7 hypertensive patients with normal renal function following α-methyldopa (1 g) orally. Five of these patients subsequently received α-methyldopa ethyl ester (250 mg) (methyldopate) intravenously and two further patients received 250 mg of α-methyldopa intravenously. After oral administration a large amount of total plasma α-methyldopa was present as sulphate conjugate. There were wide interindividual differences in the ratio of free: conjugated α-methyldopa in plasma (ratio at 4 hours ranged from 3.73 – 0.83) suggesting that individual differences in the extent of sulphate conjugation may occur. There was no close correlation between the degree of conjugation and the fall in arterial pressure. At all time intervals examined, plasma concentrations were higher following intravenous α-methyldopa than α-methyldopate. The plasma concentration of α-methyldopa (free and esterified) 60 minutes after i.v. α-methyldopate was 1.7±0.3 µg/ml wile at the same time after the same dose of methyldopa by the same route the mean concentration was 5.9 µg/ml. Although small amounts of sulphate conjugate were detected after i.v. α-methyldopate, insignificant quantities of conjugate were found after i.v. α-methyldopa. The average fall in mean arterial pressure was 27 mm Hg following i.v. α-methyldopa but only 2.7 mm Hg following α-methyldopate. These results suggest that sulphate conjugation of α-methyldopa occurs in the gastrointestinal tract during absorption. Hydrolysis of α-methyldopa ethyl ester does not appear to be instantaneous and pharmacokinetic differences between the ester and free α-methyldopa have been demonstrated.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 387-390 
    ISSN: 1432-1041
    Keywords: lupus erythematosus ; acetylation ; discoid and systemic lupus ; frequency ; distribution ; severity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetylator phenotype was measured in 58 patients presenting to a skin clinic with discoid lupus erythematosus (DLE) and in 51 normal healthy subjects. Twenty seven of the patients with DLE were found to have evidence of systemic lupus erythematosus (D+SLE). Frequency of slow acetylator phenotype was 58% in all DLE patients, 52% in those with D+SLE and was no different from the 57% in controls. The distribution of acetylator phenotypes within the groups with DLE and those with D+SLE was similar to controls.Severity of DLE was assessed as number of skin lesions and median lesion count was 11.5 in slow acetylators and 10 in fast acetylators but in D + SLE median lesion count was 22 in slow acetylators and 12 in fast acetylators, and there was a significant inverse relationship between lesion count and rate of acetylation; scores for systemic involvement showed no relationship. We conclude that there is no difference in the frequency or distribution of slow acetylator phenotype between normal subjects and patients with DLE with or without SLE but that actual rate of acetylation may determine severity of expression of the disease in slow acetylators.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 14 (1978), S. 301-304 
    ISSN: 1432-1041
    Keywords: Labetalol ; methyldopa ; comparative trial ; arterial hypertension ; β-blockade ; α-blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 20 patients (12 female) with moderately severe essential hypertension [blood pressure during placebo treatment 181±6 (systolic), 107±3 (diastolic)] completed a double-blind, cross-over dosetitrated comparison of labetalol and methyldopa. Both drugs reduced lying and standing arterial blood pressure to a similar extent, although only labetalol reduced heart rate. Compliance was high (〉95%) with both drugs, and the incidence of subjective adverse effects was similar.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 15 (1979), S. 319-322 
    ISSN: 1432-1041
    Keywords: warfarin ; anticoagulation ; age ; sex ; weight
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 228 ambulatory patients receiving treatment with warfarin, there was a progressive decline in the dose required to produce an equivalent degree of anticoagulant control with increasing age from the third decade onwards. However, the relationship between age and dose was significant only in patients receiving warfarin after episodes of venous thromboembolism or because of coronary artery disease. Patient weight was also related to warfarin requirements, although it was less important a determinant than age.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 25 (1983), S. 547-551 
    ISSN: 1432-1041
    Keywords: astemizole ; histamine weal and flare ; urticaria ; pruritus ; antihistamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of astemizole on the weal and flare response to intradermal histamine has been studied in normal volunteers after single dosing, and in patients with urticaria and pruritus after chronic dosing with the drug. Single doses of astemizole (40 mg) in normal volunteers significantly reduced histamine weal and flare at 24 and 48 h (p〈0.001). Before treatment, there was a significantly greater response to intradermal histamine in patients with urticaria than pruritus (p〈0.05). Chronic dosing with astemizole produced significant reduction in histamine-induced weal and flare in both patient groups which did not show evidence of tachyphalaxis over the period of the study. The effect of astemizole on histamine-induced weal and flare was accompanied by a significant increase in the rate of weal and flare disappearance in both patients (weal p〈0.002, flare p〈0.05) and volunteers (weal p〈0.02, flare p〈0.005); but there was no change in the rate of weal formation. The effects of astemizole on weal and flare kinetics may be a function of its high level of H1 antagonist activity.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1986), S. 485-489 
    ISSN: 1432-1041
    Keywords: esterase activity ; aspirin ; British and Ghanaian subjects ; cholinesterase ; paraoxonase ; phenylacetate esterase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have measured aspirin esterase, cholinesterase, paraoxonase, and phenylacetate esterase activities in samples of plasma from British and Ghanaian subjects. Aspirin esterase, paraoxonase, and phenylacetate esterase activities were significantly lower in Ghanaians compared with British subjects. However, cholinesterase activities were similar in Ghanaian and British plasma samples. The lower esterase activities in Ghanaian plasma samples may result in higher circulating concentrations and greater pharmacological effects of drugs such as aspirin.
    Type of Medium: Electronic Resource
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