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  • 1
    Electronic Resource
    Electronic Resource
    Berechnung einer Zusatzdosis zur Erhaltung der Serumkonzentration eines Pharmakons nach Schnellinfusion von Plasmaexpandern (1971)
    Springer
    European journal of clinical pharmacology 4 (1971), S. 54-58 
    Details
    ISSN: 1432-1041
    Keywords: pharmacokinetics ; infusion ; plasma expander ; blood level fluctuation ; sulfonamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Summary A hypothetical pharmacokinetic model is reported which describes the decreasing fluctuations in the blood levels of a sulfonamide during infusion of a plasma expander. Its concentration in the serum increases reciprocally with the amount of plasma expander infused. These procedures can be described by simple equations, and it is possible therefore, to calculate the dose required to maintain a constant blood level during the infusion.
    Notes: Zusammenfassung Es wird über ein hypothetisch-pharmakokinetisches Modell berichtet, welches sich mit der absinkenden Serumkonzentration eines Sulfonamids nach Infusion eines Plasmaexpanders beschäftigt. Die Serumkonzentration fällt reziprok zur infundierten Menge des Plasmaexpanders ab. Die Vorgänge lassen sich durch einfache Gleichungssysteme beschreiben. Es gelingt daher, eine Zusatzdosis zu berechnen, welche den bei Infusionsbeginn bestehenden Plasmaspiegel annähernd konstant erhält.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00568900
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  • 2
    Electronic Resource
    Electronic Resource
    Subjective symptoms and pharmacokinetics/dynamics of metoprolol CR in elderly subjects — a comparison with atenolol (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 571-578 
    Details
    ISSN: 1432-1041
    Keywords: Atenolol ; metoprolol CR ; elderly subjects ; subjective symptoms ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, randomised, cross-over study, the pharmacokinetic/dynamic effects and subjective symptoms of a new controlled-release (CR) formulation of metoprolol (50 and 100 mg) have been compared with atenolol (50 mg) and placebo in 20 elderly healthy subjects. The metoprolol CR formulation displayed an even plasma concentration-time profile over the dosage interval while atenolol produced a peak at 2–4 h. All three active treatments produced significant β1-blockade at 24 h compared to placebo. Four hours after dose intake, the degree of β1-blockade was significantly greater with conventional atenolol 50 mg than with either dose of metoprolol CR. Subjective well-being was examined with a self-administered questionnaire (MSE-profile), including three dimensions: Contentment, Vitality and Sleep. No significant differences were detected between placebo and either dose of metoprolol CR. At 2 h, following atenolol, a deterioration in Vitality was observed compared to placebo and metoprolol CR 100 mg. At the end of the dosage interval there was no longer any significant difference between the treatments. Perceived leg fatigue during exercise, evaluated 4 h after dosing, was more pronounced during treatment with atenolol than metoprolol CR 50 mg. The results suggest that the metoprolol CR formulation was not associated with significant effects on subjective well-being, whereas atenolol caused a deterioration at the time of the peak plasma concentration of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278584
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  • 3
    Electronic Resource
    Electronic Resource
    Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 277-281 
    Details
    ISSN: 1432-1041
    Keywords: Key words Pantoprazole; Proton pump inhibitor drug interaction ; oral anticoagulant phenprocoumon ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Pantoprazole is a selective proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzymes in man. Due to the clinical importance of an interaction with anticoagulants, this study was carried out to investigate the possible influence of pantoprazole on the pharmacodynamics and pharmacokinetics of phenprocoumon. Methods: Sixteen healthy male subjects were given individually adjusted doses of phenprocoumon to reduce prothrombin time ratio (Quick method) to about 30–40% of normal within the first 5–9 days and to maintain this level. The individual maintenance doses remained unaltered from day 9 on and were administered until day 15. Additionally, on study days 11–15, pantoprazole 40 mg was given per once daily. As a pharmacodynamic parameter, the prothrombin time ratio was determined on days 9 and 10 (reference value) and on days 14 and 15 (test value), and the ratio test/reference was evaluated according to equivalence criteria. Results: The equivalence ratio (test/reference) for prothrombin time ratio was 1.02 (90% confidence interval 0.95–1.09), thus fulfilling predetermined bioequivalence criteria (0.70–1.43). The pharmacokinetic characteristics AUC0–24h and Cmax of S(−)-and R(+)-phenprocoumon were also investigated using equivalence criteria. Equivalence ratios and confidence limits of AUC0–24h and of Cmax of S(−)-phenprocoumon (0.93, 0.87–1.00 for AUC0–24h; 0.95, 0.88–1.03 for Cmax) and of R(+)-phenprocoumon (0.89, 0.82–0.96; 0.9, 0.83–0.98) were within the accepted range of 0.8–1.25. Conclusion: Pantoprazole does not interact with the anticoagulant phenprocoumon on a pharmacodynamic or pharmacokinetic level. Concomitant treatment was well tolerated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050198
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  • 4
    Electronic Resource
    Electronic Resource
    Gastric potential difference as a model in clinical pharmacology: Assessment of gastric mucosal response to aspirin (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 147-151 
    Details
    ISSN: 1432-1041
    Keywords: gastric potential difference ; aspirin ; gastric mucosal barrier ; Reizindex ; gastric irritation model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Gastric potential difference in 16 healthy subjects (GPD) was measured on three different days to assess baseline variability. The effect of three different doses of aspirin on GPD in 19 additional subjects was determined. Several new parameters are suggested for better description of the GPD changes following ingestion of known gastric irritants. From these parameters, a Reiz Index1 (RI) was calculated as a single term representing the extent and severity of the GPD response to aspirin. One-way Anova followed by Scheffe comparisons showed significant differences between the mean RI values resulting from the administration of aspirin 250, 500 and 1000 mg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542460
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  • 5
    Electronic Resource
    Electronic Resource
    Concomitant administration of the α-glucosidase inhibitor voglibose (AO-128) does not alter the pharmacokinetics of glibenclamide (1997)
    Springer
    European journal of clinical pharmacology 53 (1997), S. 149-152 
    Details
    ISSN: 1432-1041
    Keywords: Key words Voglibose; glibenclamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Voglibose is a new and potent inhibitor of α-glucosidases used for treatment of diabetes mellitus. It increases gastro-intestinal motility and could thus affect absorption of other concurrently administered antidiabetic drugs. The aim of this study was to investigate whether or not voglibose modifies the pharmacokinetics of glibenclamide, a widely used oral antidiabetic, and the glibenclamide-induced decrease in fasting serum glucose. Methods: Twelve healthy male subjects were included in this double-blind cross-over study and received a single 1.75-mg dose of glibenclamide on the 8th day of continuous administration of either placebo (reference) or voglibose 5 mg t.i.d. (test). Blood samples were taken to determine the pharmacokinetic characteristics of gliben-clamide and the test/reference ratios were evaluated according to bioequivalence criteria. Additional blood samples were taken to measure serum glucose on the same day. Results: The concentration–time course of glibenclamide under concomitant voglibose administration was similar to that under placebo. The equivalence ratio (test/reference) for the pharmacokinetic characteristics AUCnormwas 1.03 (geometric mean; 0.95–1.11, 90% confidence interval) and Cmax,norm1.01 (0.94–1.08). The parameters were within the accepted range of 0.8–1.25 (AUC) or 0.7–1.43 (Cmax), thus fulfilling equivalence criteria and indicating no effect of voglibose on glibenclamide kinetics. The glibenclamide-induced decrease in fasting serum glucose concentration was similarly independent of placebo or voglibose co-administration. Conclusions: Voglibose did not interact with glibenclamide on a pharmacokinetic level. Concomitant treatment was well tolerated and has been proven to be safe for further clinical use.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050354
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  • 6
    Electronic Resource
    Electronic Resource
    The α-glucosidase inhibitor voglibose (AO-128) does not change pharmacodynamics or pharmacokinetics of warfarin (1997)
    Springer
    European journal of clinical pharmacology 53 (1997), S. 153-157 
    Details
    ISSN: 1432-1041
    Keywords: Key words Warfarin enantiomers ; Voglibose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Voglibose is a new and potent inhibitor of α-glucosidases and is used for the treatment of diabetes mellitus. Since voglibose increases gastrointestinal motility and could thus affect absorption of concomitantly administered drugs, it was investigated whether or not voglibose modifies the pharmacodynamics and pharmacokinetics of warfarin, an oral anticoagulant frequently used in cardiovascular disorders likely to arise in diabetic patients. Methods: Twelve healthy male subjects were given individually adjusted doses of warfarin to reduce prothrombin time (Quick's method) to a value of about 30–40% of the normal range within the first 8 days. Then, the individual maintenance dose, given in the morning, was maintained until day 15. On study days 11–15, voglibose was co-administered per os in a dose of 5 mg t.i.d. The prothrombin time was determined on days 10 and 11 (reference) and on days 15 and 16 (test), and the steady-state pharmacokinetic characteristics of the warfarin enantiomers were determined on days 10 (reference) and 15 (test). The ratios test/reference were evaluated according to bioequivalence criteria. Results: The equivalence ratio (test/reference) for the pharmacodynamic parameter prothrombin time was 0.97 and for the pharmacokinetic characteristics AUC0–24 h,τ,ss: S-(−)-warfarin, 1.05; R-(+)-warfarin, 1.01; and Cmax,ss: S-(−)-warfarin, 1.08; R-(+)-warfarin, 1.04. All parameters were within the predetermined accepted range of 0.7–1.43 (pharmacodynamics) or 0.8–1.25 (pharmacokinetics), thus fulfilling equivalence criteria. Conclusions: Voglibose modified neither the pharmacodynamics nor the pharmacokinetics of warfarin under steady-state conditions. Concomitant treatment was well tolerated and has been proven to be safe for further clinical use.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050355
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