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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of nimodipine in patients with aneurysmal subarachnoid haemorrhage (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 421-425 
    Details
    ISSN: 1432-1041
    Keywords: nimodipine ; subarachnoid haemorrhage ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Patients with a ruptured supratentorial aneurysm undergoing early surgery after the subarachnoid haemorrhage were treated postoperatively with nimodipine to prevent delayed ischaemic dysfunction. It was given first as a continuous intravenous infusion 2 mg/h (mean dose 0.5 µg/kg/min) for at least 7 days, and then orally (45 mg × 6) for at least a further 7 days. During the i.v. infusion, the mean plasma concentration was 26.6±1.8 ng/ml. The plasma clearance ranged from 0.57 to 1.77 l/kg/h and was negatively correlated with the age of the patient. Immediately prior to successive oral doses, the mean plasma concentration was 13.2 ng/ml (range〈3–38.8 ng/ml). The peak level was usually found after 1 h; it ranged from 7.0–96.0 ng/ml. Mean bioavailability was 15.9%. The nitropyridine metabolite was found in measurable concentrations only after oral treatment with nimodipine. In some cases, the concentration of metabolite exceeded that of the parent compound. The three patients investigated who developed delayed ischaemic dysfunction had plasma concentrations well within the range in patients who did not, so it seems unlikely that the therapeutic failure could be attributed to individual deviations in the pharmacokinetics of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607954
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    The interaction of erythromycin with theophylline (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 493-498 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; erythromycin ; drug interaction ; aminophylline ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the interaction of erythromycin with theophylline. We gave ten healthy volunteers theophylline as an intravenous loading dose (5 mg·kg−1) over 1 h, followed by a maintenance infusion (0.5 mg·kg−1·h−1) for 5 h. A second infusion of theophylline was given after 9 days of treatment with 1 g erythromycin base daily, and the concentrations of theophylline were determined during the infusion periods. The concentrations of erythromycin were measured for 8 h, after one week of treatment, and also after the last erythromycin dose, simultaneously with the second theophylline infusion. Concentrations within the therapeutic range were obtained with both drugs. A significant increase in both AUC and mean plasma concentrations of theophylline was seen during erythromycin treatment. The plasma clearance of theophylline was reduced in 9 of the 10 subjects. Renal clearance increased correspondingly, but the change was not statistically significant. Serum concentrations of erythromycin fell significantly, by more than 30%, with concurrent theophylline medication. We conclude that an interaction between theophylline and erythromycin, affecting both drugs, can be shown with concentrations of the drugs within the therapeutic range.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637676
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Dopamine D2 blocking activity and plasma concentrations of remoxipride and its main metabolites in the rat (1993)
    Springer
    Journal of neural transmission 93 (1993), S. 187-203 
    Details
    ISSN: 1435-1463
    Keywords: Hypothermia ; DA D2 receptors ; FLA 797(−) ; FLA 908(−) ; NCQ 436(−) ; remoxipride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Remoxipride and its active metabolites, the phenolic compounds FLA 797(−) and FLA 908(−) and the catecholic NCQ 436(−) and haloperidol, were examined for their ability to block hypothermia in the rat induced by dopamine (DA) D2 receptor stimulation. In addition, plasma levels of remoxipride and its active metabolites were measured using HPLC methods. Remoxipride (1 μmol/kg), given 30 or 15 min prior to, or 5 and 15 min after, the DA agonists, blocked the hypothermia induced by the DA D2 receptor agonists quinpirole (0.25mg/kg s.c.) and pergolide (0.1 mg/kg s.c). Administration of remoxipride by the i.v. or s.c. routes was more effective than by the i.p. route. FLA 797(−), FLA 908(−), and haloperidol were more effective than remoxipride in preventing the hypothermia caused by quinpirole, while NCQ 436(−) was less effective than remoxipride. The variation in time of remoxipride's action and effectiveness in blocking the induced hypothermia followed the variations in plasma concentrations. The plasma concentrations of the active metabolites were below the limit of determination (〈2 nmol/l). Based on estimation of free brain concentrations at effective dose levels together with in vitro affinities for the DA D2 receptor it was concluded that the metabolites FLA 797(−), FLA 908(−), and NCQ 436(−) do not appear to contribute to the antagonism of DA D2 mediated neurotransmission following a low remoxipride dose (1 μmol/kg).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01244996
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  • 4
    Electronic Resource
    Electronic Resource
    Concentrations of remoxipride and its phenolic metabolites in rat brain and plasma. Relationship to extrapyramidal side effects and atypical antipsychotic profile (1993)
    Springer
    Journal of neural transmission 94 (1993), S. 199-216 
    Details
    ISSN: 1435-1463
    Keywords: Bar test ; catalepsy ; remoxipride ; phenolic metabolites ; haloperidol ; plasma ; brain ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cataleptic effect of remoxipride was examined in the horizontal bar test after i.v.,i.p. and s.c. administration to male rats. Remoxipride induced immediate catalepsy after high i.v. doses (ED50=49 μmol/kg) while peak effects were seen 60–90 min after i.p. administration (ED50=38 μmol/kg). Following s.c. administration remoxipride failed to produce a statistically significant catalepsy in the 20–100 μmol/kg dose range (ED50 〉 100 μmol/kg). In contrast, haloperidol was found to be more effective in inducing catalepsy after i.v. (ED50=0.4 μmol/kg) than after i.p. or s.c. administration (ED50=0.9 μmol/ kg). The atypical antipsychotic profile of remoxipride was more pronounced when the compound was given i.v. or s.c. as compared with the i.p. route. Plasma and brain (striatum and nucleus accumbens) concentrations of remoxipride and its active phenolic metabolites FLA 797(−) and FLA 908(−) were measured by high performance liquid chromatography. The 40 μmol/kg dose of remoxipride resulted in plasma and brain concentrations of remoxipride which were 300–1000-fold higher (depending on the route of administration) than the most potent of the phenolic metabolites, e.g., FLA 797(−). The plasma and brain concentrations of remoxipride and its phenolic metabolites were related to DA D2 receptor blocking potency and to the temporal course and effectiveness to induce catalepsy. This analysis suggested that the unbound concentrations of the phenolic metabolites were too low to play a major role in the DA blocking action of remoxipride. However, FLA 797(−) may contribute marginally to the cataleptic effects following high (i.p.) doses of remoxipride.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01277025
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