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  • 1
    Electronic Resource
    Electronic Resource
    Determinanten von Digoxin-und Digitoxinplasmakonzentrationen bei älteren Patienten (1987)
    Springer
    Journal of molecular medicine 65 (1987), S. 1073-1080 
    Details
    ISSN: 1432-1440
    Keywords: Digoxin derivatives ; Digitoxin ; Variables determining plasma concentration ; Multiple linear regression analyses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 1063 patients (≥60 years, 531 men, 532 women) the plasma concentration during digitalis maintenance therapy (metildigoxin, n=356, beta-acetyldigoxin, n=359, and digitoxin, n=348) was determined and related to sex, age, body weight, serum potassium, renal function and the prescribed daily maintenance dose. Classification of treatment groups according to renal function (Crea ≤1.3 mg/dl//〉 1.3 mg/dl) did not show any difference of the mean maintenance doses. In multiple linear regression analyses only a weak relationship between plasma digitalis concentration and the studied variables was found, which could be equally attributed to dose, creatinine and serum potassium in the digoxin derivative groups, whereas for digitoxin only body weight had a significant effect on the plasma concentration. During a maintenance dose of 0.07 or 0.1 mg/die which was given to 87% of patients in the digitoxin group, 70% were found to have plasma levels within the therapeutic range.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01736113
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  • 2
    Electronic Resource
    Electronic Resource
    Beta-blocker induced changes in the cholesterol: High-density lipoprotein cholesterol ratio and risk of coronary heart disease (1984)
    Springer
    Journal of molecular medicine 62 (1984), S. 843-849 
    Details
    ISSN: 1432-1440
    Keywords: Beta-blockers ; Cholesterol ratio ; High-density lipoprotein cholesterol ; Coronary heart disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The lowering of blood pressure with beta-blocking drugs has had a low impact on coronary heart disease (CHD) mortality and the question has been raised whether adverse changes in plasma lipoproteins offset the benefits of blood pressure reduction. Comparison of plasma lipoprotein concentrations in hypertensive patients treated with commonly used beta-blockers with lipoprotein concentrations in patients with coronary heart disease shows that these drugs cause clinically important shifts in the cholesterol ratio [total cholesterol (TC): high-density lipoprotein cholesterol (HDLC)] and reductions in the atheroprotective lipoprotein HDLC. The magnitude of these changes is sufficient to increase the risk of heart attack two- to four-fold depending on the initial cholesterol ratio and the duration of treatment. Only beta-blockers with marked intrinsic sympathomimetic agonist activity (pindolol) or combined alpha-beta-blocking properties (Labetalol) appear free of adverse effects on plasma lipoproteins and triglycerides. Chronic treatment with other betablockers should be accompanied by cholesterol and HDLC measurements at the beginning of therapy. Plasma lipoprotein measurements at 3–6 month intervals seem mandatory in patients with cholesterol values greater than 6 mmol/l (230 mg/dl) and (TC):HDLC ratios above 5 at the start of treatment. The risk of a coronary event must be regarded as unacceptable when the cholesterol ratio exceeds a critical value of about 6. Further controlled studies are needed to evaluate the effects of beta-blockers in hypertension when administered for periods of up to a year or more. More information is required on the behaviour of lipoprotein subspecies and apoproteins. Since the changes in lipoproteins reported in studies referred to in this review may have been submaximal the risks and the benefits from beta-blocker therapy must be carefully considered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01711998
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Influence of serum protein binding on the uptake and retention of idarubicin by sensitive and multidrug resistant human leukemic cells (1999)
    Springer
    European journal of clinical pharmacology 55 (1999), S. 369-373 
    Details
    ISSN: 1432-1041
    Keywords: Key words Multidrug resistance ; Protein binding ; Idarubicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The objectives of the investigations were (1) to determine the binding characteristics of idarubicin (IDA) in human serum and cell culture solutions, (2) to determine the effect of protein binding on the uptake and retention of IDA by human leukemic cell lines in culture and the extent to which R-verapamil (R-VRP), an inhibitor of the P-glycoprotein (P-gp) transporter, can modulate these processes, and (3) to assess the importance of protein binding on cytostatic and chemosensitizer action in vivo. Methods: The protein binding of IDA was determined using equilibrium dialysis. Cell uptake of IDA was measured using sensitive and P-gp-containing resistant human leukemic cell lines (HL-60 and HL-60-Vinc) in vitro. IDA was assayed spectrophotofluorometrically. Results: In the incubation media examined, the free fraction of IDA varied more than seven-fold from approximately 60% in 15% fetal calf serum (FCS)/PBS to only 8% in human serum. Cellular uptake of IDA was approximately three times higher in medium containing low protein concentrations. R-VRP eliminated the difference in IDA uptake between resistant and sensitive cell lines and this was the case when the cells were incubated in solutions containing both high and low protein concentrations. However, R-VRP did not overcome the effect of high protein concentrations on IDA uptake. Conclusions: Plasma protein binding is an important determinant for cellular uptake of IDA in vitro. This should be taken into account when interpreting results of in vitro functional assays with patient material. Chemosensitizers such as R-VRP are effective in both high and low protein solutions. Investigations like these may be useful for evaluating cytostatic efficacy and chemosensitizer action in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050642
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  • 4
    Electronic Resource
    Electronic Resource
    Verapamil and drug metabolism by the cytochrome P450 isoform CYP1A2 (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 463-464 
    Details
    ISSN: 1432-1041
    Keywords: Verapamil ; Cytochrome P450 ; theophylline ; CYP1A2 ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280138
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  • 5
    Electronic Resource
    Electronic Resource
    24-hour anti-ischaemic action with once daily nifedipine (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 587-590 
    Details
    ISSN: 1432-1041
    Keywords: Nifedipine, Coronary artery disease ; slow release, ST-segment depression, adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The ability of a fatty-alcohol matrix, slow-release tablet of nifedipine 60 mg to maintain a 24-hour antiischaemic action in the fixed dose of 60 mg once daily has been investigated in a randomised, placebo-controlled, double-blind trial. 12 normotensive patients with angiographically proven coronary artery disease (stenosis of at least one major vessel ≥ 70%) were studied. The anti-ischaemic response was assessed over a period of 4 days as changes in the exercise-induced ST-segment depression 6 h and 24 h postdose, and ST segment changes in 24-h ambulatory ECGs. A measurable anti-ischaemic response was observed in 8 of the 12 patients. Exercise-induced ST-segment depression 6 h after the administration of nifedipine was reduced by 30% compared to placebo, and there was still a measurable anti-ischaemic response 24-h post-dosing. Both responses were independent of changes in exercise blood pressure. In 7 patients with ischaemic episodes in the 24-h ECGs, nifedipine treatment had only a minor effect on the intensity and duration of ischaemia. It is concluded that a significant anti-ischaemic effect lasting 24 h could be demonstrated using effort-induced ST-segment changes in patients with angiographically proven coronary heart disease, who were treated once daily with nifedipine 60 mg as a fatty-alcohol slow release tablet.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02284955
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  • 6
    Electronic Resource
    Electronic Resource
    The pharmacological properties and clinical use of valdecoxib, a new cyclo-oxygenase-2-selective inhibitor (2003)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 17 (2003), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cyclo-oxygenase-2-selective inhibitors produce less gastric damage than conventional non-steroidal anti-inflammatory drugs. Valdecoxib is a new orally administered cyclo-oxygenase-2-selective inhibitor, recently approved for use in osteoarthritis, rheumatoid arthritis and primary dysmenorrhoea in the USA. The drug has been evaluated in more than 60 clinical studies involving more than 14 000 patients and healthy volunteers. The analgesic efficacy of valdecoxib at a dose of 10 mg once daily in both osteoarthritis and rheumatoid arthritis is superior to that of placebo and similar to that of traditional non-steroidal anti-inflammatory drugs. Valdecoxib is effective in single doses of up to 40 mg for the alleviation of acute menstrual pain and has a rapid onset of action (within 30 min) and a long duration of analgesia (up to 24 h). Valdecoxib is well tolerated and has safety advantages compared with traditional non-steroidal anti-inflammatory drugs in terms of less gastrointestinal toxicity and a lack of an effect on platelet function. The incidence of adverse effects involving the kidney (fluid retention, oedema and hypertension) is similar to that of non-selective, non-steroidal anti-inflammatory drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2003.01460.x
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