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  • 1
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of a new radiosensitiser, Ro 03-8799 in humans (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 483-489 
    Details
    ISSN: 1432-1041
    Keywords: radiosensitiser ; pharmacokinetics ; healthy volunteers ; tumour patients ; Ro 03-8799
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A new hypoxic cell radiosensitiser, Ro 03-8799 has been administered intravenously to human volunteers and its kinetic parameters derived from plasma and urine data. Good penetration of drug into tumour tissue is found, consistent with its large volume of distribution. The plasma clearance of this compound is rapid due to high metabolic and renal clearances. These parameters combine to produce an elimination half-life of 5.6 h, approximately half that of misonidazole, a well studied radiosensitiser. It is hoped that this decrease in total body exposure will also reduce the cumulative toxicity seen when misonidazole is administered repeatedly.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00549599
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  • 2
    Electronic Resource
    Electronic Resource
    Dosage regimen of cimetidine reviewed. Possible drug accumulation after multiple oral doses (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 539-542 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; dosage regimen ; multiple oral doses ; accumulation ; pharmacokinetics ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The doses of cimetidine recommended differ in children, especially those with cystic fibrosis. These dosage regimens were derived from single-dose pharmacokinetic studies of the drug. Some authors showed, however, that after administration of repeated oral doses of cimetidine in healthy adults and children with cystic fibrosis, the elimination half-life of the drug was markedly prolonged. In view of the ability of cimetidine to inhibit metabolism of other drugs, it is suggested that the parent compound and/or its metabolite(s) may inhibit its own metabolism during a prolonged course of treatment. Enterohepatic recirculation of the drug and/or its metabolite(s) may also contribute to prolongation of its elimination. One should therefore be cautious in using single-dose pharmacokinetic parameters to calculate repeated dose regimens and expected plasma steady-state concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00615214
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  • 3
    Electronic Resource
    Electronic Resource
    Diuretic effect and disposition of furosemide in cystic fibrosis (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 333-341 
    Details
    ISSN: 1432-1041
    Keywords: Furosemide ; cystic fibrosis ; pharmacokinetics ; diuretic effect ; baseline urine flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacodynamics and kinetics of single oral and intravenous doses of furosemide were studied in 9 patients (mean age 18.5 y) with cystic fibrosis. The diuretic effect of furosemide lasted for 6 h after oral administration and 2 h following intravenous injection of the drug. The patients with cystic fibrosis had a more pronounced diuretic response both to the oral and intravenous treatments than that reported in normals. Furosemide caused a marked decrease in urine pH for 5 h following the oral dose and between the 2nd and 3rd h after i.v. injection. The baseline nocturnal urine flow rate in 7 of the 9 patients given furosemide orally was increased by 30.6% compared to that reported in healthy subjects. The bioavailability of furosemide, its mean absorption rate and the mean plasma and urinary elimination half-lives both of the oral and the intravenous drug were similar to those reported in normal subjects. The patients with cystic fibrosis showed, however, about double normal mean total clearance after both the oral and i.v. treatments, and its renal clearance was almost half the plasma clearance. Nonrenal clearance was markedly increased in the patients, which agreed with a considerable decrease in the renal excretion of the drug. The mean apparent volume of distribution was also markedly increased compared to data in the literature. Oral furosemide resulted in a moderate increase in haematocrit and haemoglobin levels in 7 of 9 patients with cystic fibrosis and marked hypokalemia developed in 6 of the 9 patients 6 h after dosing. Pulmonary function tests performed at that time were changed in an inconsistent manner. The sweat test was significantly perturbed in those subjects, although the concentration of chloride in sweat did not fall below 60 mEq/l in any of the sweat samples tested.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265840
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  • 4
    Electronic Resource
    Electronic Resource
    Influence of food on the bioavailability and some pharmacokinetic parameters of diprafenone – a novel antiarrhythmic agent (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 315-319 
    Details
    ISSN: 1432-1041
    Keywords: Key words Diprafenone; antiarrhythmics ; bioavailability ; human ; foods ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The present study was done to investigate the effect of food on the bioavailability of diprafenone. Methods: The most important pharmacokinetic parameters (Cmax, t1/2, AUC) and the relative oral availability of a solid oral preparation of racemic diprafenone were investigated when administered to fasting subjects and 10 min after a standard meal, in an open, randomised, crossover trial. Single oral doses of 100 mg were given on two different occasions, at least 1 week apart. The serum concentrations of diprafenone and its hydroxy-metabolite were determined up to 24 hours after administration by a sensitive, specific HPLC method. Fifteen healthy, male volunteers were enrolled in the trial. Their mean height, weight and age were 183 cm, 80 kg and 22 years, respectively. Fourteen volunteers were found to be rapid hydroxylators and one was a slow hydroxylator of debrisoquine. Only data from the rapid hydroxylators were used in the statistical analysis. Results: Food increased the oral bioavailability of diprafenone by approximately 50%. This effect was similar in rapid and in slow hydroxylators. The only slow hydroxylator in this trial had an AUC0–last ratio (with food/fasting) of 1.54. These findings suggest that diprafenone should be administered in a constant temporal relationship to food.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050115
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