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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 9 (1976), S. 367-372 
    ISSN: 1432-1041
    Keywords: Sotalol ; β-adrenoceptor blocking drugs ; exercise tachycardia ; efficacy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of sotalol after oral administration were measured on the tachycardia induced by strenuous exercise in normal subjects. Plasma sotalol levels were also determined. The oral administration of sotalol (50, 100, 200 and 400 mg) to 6 subjects produced a progressive reduction in the tachycardia induced by severe exercise. This was similar to the effects of 25, 50, 100, 200, 400 and 800 mg given to different subjects. Each increase in sotalol dose produced a successively greater reduction in exercise tachycardia. This did not appear to be maximum even with 800 mg. Oral sotalol was rapidly absorbed and produced peak blood levels in 2 – 3 hours. The plasma levels of sotalol measured 2 hours after the oral administration of 25 to 800 mg showed never more than a six-fold variation between different subjects. The half-life of sotalol in plasma was 12.7 ± SE 1.6 hours. There was a significant correlation between the logarithm of the plasma sotalol concentration and the percentage reduction of exercise heart rate. It is concluded that the oral administration of sotalol either once or twice daily (depending on dose level) will provide satisfactory 24-hour blockade of β-adrenoceptors.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 13 (1978), S. 29-33 
    ISSN: 1432-1041
    Keywords: Microcrystalline theophylline ; chronic obstructive airways disease ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma theophylline concentrations have been measured in 9 patients with chronic obstructive airways disease following the oral administration of a microcrystalline theophylline preparation. Some measurements of FEV1 were also made. Four patients were given 375 mg as a single dose and then subsequently 375 mg stat and 125 mg 4 times daily for 3 days, (Group I). A further 5 patients took 250 mg as a single dose and then 250 mg 4 times daily for 3 days, (Group II). In both groups, following the single dose and again after the last dose of chronic administration, blood samples were obtained at frequent intervals up to 24 h for plasma drug estimation. During the 3-day course, blood samples were drawn before and 2 h after each morning dose. In Group I patients, substantial plasma theophylline concentrations were seen only after the loading dose. Thereafter, the mean concentrations before or 2 h after the morning doese were always less than 4.0 µg/ml. Trough concentrations were usually below 2.0 µg/ml. In contrast patients in Group II achieved substantially higher plasma theophylline concentrations, with mean peak concentrations always 10 µg/ml or greater, and trough concentrations greater than 5 µg/ml on at least one occasion in every subject. The elimination half-lives after chronic administration in both groups were not significantly different from those obtained after single doses. Mean drug accumulation, measured as AUCss/AUC1, was 0.87±0.07 in Group I and 0.72±0.14 in Group II, indicating that accumulation had not occurred with either regimen. The mean increase in FEV1 2 h after the administration of a single dose was 19.2% after 375 mg and 16.7% after 250 mg. These results indicate that the recommended dosage regimen for microcrystalline theophylline preparation (375 mg stat and 125 mg 4 times daily) produces inadequate plasma theophylline concentrations: 250 mg 4 times daily would appear to be likely to result in satisfactory theophylline levels in more patients.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 29 (1985), S. 323-329 
    ISSN: 1432-1041
    Keywords: lignocaine ; pharmacokinetics ; proteinbinding ; indocyanine green ; ageing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single dose studies were performed in six young and six elderly nonsmokers using lignocaine as a model drug with high intrinsic clearance. Subjects received lignocaine 250 mg orally and 50 mg intravenously in random order and drug concentrations in blood and plasma were measured for up to 8 h after dose. Protein binding was estimated at 37 °C by equilibrium dialysis. Indocyanine green kinetics were also calculated in each individual following 0.15 mg/kg intravenously. Bioavailability of lignocaine was greater in the elderly but there was no apparent difference in the rate of absorption. Intrinsic clearance of lignocaine was lower in the aged. Elimination half-life was longer in the elderly but there was no significant difference in apparent volume of distribution or systemic clearance of lignocaine. Plasma clearance of indocyanine green showed no correlation with systemic lignocaine clearance and was lower in the aged subjects. Blood/plasma lignocaine ratio was less than unity in both groups. Binding of lignocaine to plasma proteins showed concentration-dependence and was higher in the geriatric group. Maximum binding capacity of lignocaine was greater in the elderly but the binding affinity did not significantly change with age. Greater oral bioavailability of drugs like lignocaine may produce higher plasma concentrations in the elderly. Unlike indocyanine green, the systemic clearance of lignocaine was unaltered by age in this group of non-smokers. The protein-binding of lignocaine, like many other basic drugs, is increased in elderly subjects.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: angiotensin II ; captopril ; platelet receptor density ; vascular responses ; long term treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The density of angiotensin II (Ang II) receptors on the platelet and the vascular responsiveness to infused angiotensin II before and after two weeks of captopril therapy were examined in ten healthy male volunteers. There was a significant increase in blood flow to the forearm, but no significant changes in either the density of angiotensin II receptors or the pressor response to infused angiotensin II following captopril therapy. The study demonstrates that long term reduction of angiotensin II formation by captopril in man does not increase the responsiveness of the receptors to infused angiotensin, nor results in an „up regulation“ of the angiotensin receptors. It also provides further evidence that some of the long term vasodilator effects of captopril may be mediated by mechanisms other than inhibition of angiotensin I (Ang I) converting enzyme.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 383-388 
    ISSN: 1432-1041
    Keywords: naproxen ; sustained-release formulation ; pharmacokinetics ; bioavailability ; efficacy ; tolerability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and clinical efficacy of a once-daily sustained-release formulation of naproxen (sodium salt) have been compared with those of conventional-release agents. In a single dose pharmacokinetic study, the rate of absorption of the sustained-release preparation was less than that of a conventional-release preparation but the extent of absorption was the same. As is the case with conventional-release naproxen, food decreased the rate but not the extent of absorption of the sustained-release formulation. On multiple dose administration for 7 days, the AUC and average concentrations of the sustained release preparation (1 g daily) were the same as those for conventional release preparations of naproxen sodium (250 mg four times daily) and naproxen free acid (500 mg daily). The conventional-release sodium salt was absorbed more quickly with no differences in bioavailability. A double-blind clinical comparison in patients with osteoarthritis showed the sustained-release preparation (1 g daily) to be equivalent in efficacy to conventional naproxen capsules (500 mg twice daily) but to have a significantly lower incidence of gastrointestinal side-effects. The results suggest that sustained-release naproxen sodium has potential for use as a once-daily treatment for inflammatory disease.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1041
    Keywords: acetyl-L-carnitine ; renal clearance ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of acetyl-L-carnitine hydrochloride were investigated in 6 healthy volunteers of both sexes after i.v. injection of 500 mg of the drug, expressed as inner salt. Plasma concentrations and urinary excretion of acetyl-L-carnitine (A), L-carnitine (B) and total acid soluble L-carnitine fraction were evaluated over a period lasting from 24 h before to 48 h after the administration. Plasma concentrations of A increased quickly after administration and then declined reaching base values within 12 h. Conversely, plasma concentrations of B rose more slowly, reaching a peak in 30–60 min, and then declined to base values within 24 h. Most of the injected dose of acetyl-L-carnitine was recovered in the urine during the first 24 h after administration as B and A. Mean renal clearance of both A and B during the first 12 h after injection was higher than the base values, suggesting the presence of a saturable tubular reabsorption process which may counterbalance major changes occurring in plasma concentrations of L-carnitine pattern.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 21 (1981), S. 169-172 
    ISSN: 1432-1041
    Keywords: tolmesoxide ; vasodilator ; heart failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects and pharmacokinetics of single intravenous doses of tolmesoxide, a new vasodilator agent, were studied in 6 patients with severe cardiac failure secondary to ischaemic cardiomyopathy and refractory to concentional therapy. The mean (±SEM) baseline cardiac index (CI) and pulmonary artery diastolic pressure (PADP) were 1.7±0.11/ min/m2 and 30.5±4.1 mm Hg respectively. The mean % rise in CI was 78.8±23.3 and the mean % fall in PADP was 35.2±5.2. The mean half life of tolmesoxide in these patients was markedly prolonged at 15.6±6.6h. Side effects were minimal — vomiting was seen in 1 patient. This agent warrants further study in the long term management of refractory cardiac failure.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 23 (1982), S. 93-97 
    ISSN: 1432-1041
    Keywords: tolmesoxide ; vasodilator ; hypertension ; pharmacokinetics ; haemodynamics ; plasma renin activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic response and pharmacokinetics of single dose oral tolmesoxide were studied at various dose levels in 4 patients with severe hypertension. There was a reproducible fall in mean arterial pressure from baseline of 24.2% and a rise in heart rate of 37.6% following administration of tolmesoxide. The onset of antihypertensive action occurred within 1 h, with a peak effect at 3 h after dosing. The mean duration of action was up to 12.0 h. Tolmesoxide had a mean half-life of 3.0 h. It was rapidly absorbed with a mean peak plasma level occurring at 1.0 h. Plasma levels correlated well with the doses administered. Side-effects included mild nausea, facial flushing and postural symptoms.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 38 (1990), S. 99-99 
    ISSN: 1432-1041
    Keywords: enalapril ; milk ; enalaprilat ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 38 (1990), S. 309-312 
    ISSN: 1432-1041
    Keywords: Acetyl-L-carnitine ; renal impairment ; pharmacokinetics ; adverse reactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetyl-L-carnitine 1.5 g and 3.0 g was administered as three divided doses on each of two occasions to 24 people with varying renal failure (creatinine clearance 127 – 8 ml·min−1). Plasma and urinary concentrations of total-L-carnitine, free (non-esterified) carnitine, short-chain esters and acetyl-L-carnitine were measured. The baseline (pre-study) concentrations of all four substances were related to renal function. Patients whose creatinine clearance was below about 30–40 ml·min−1 were had the highest concentrations. Renal elimination of all four substances was related to dose and to renal function. There was evidence for dose-related elimination, with greater elimination of the larger dose.
    Type of Medium: Electronic Resource
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