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  • healthy volunteers  (54)
  • lipid peroxidation  (34)
  • Springer  (88)
  • 2005-2009
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  • 1980-1984  (28)
  • 1965-1969
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  • 1
    ISSN: 1420-9071
    Schlagwort(e): Lipopeptides ; immunomodulation ; cytochrome P-450 ; lipid peroxidation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Immunomodulating lipopeptides lauroyl-L-Ala-γ-D-Glu-LL-A2pmNH2-Gly (RP 44.102) and lauroyl-L-Ala-γ-D-Glu-LL-A2pmNH2 (RP 56.142) were found to protect mice against the hepatotoxicity of paracetamol, which is due to cytochrome P-450 dependent formation of toxic metabolites and radicals. In fact they decreased the amount of hepatic microsomal cytochrome P-450, and the level of CCl4-induced lipid peroxidation. In contrast lauroyl-L-Ala-γ-D-Glu-DD-A2pmNH2 (RP 53.204), which only differs by the configuration of the two chiral carbons of A2pm (diaminopimelic acid) and is not an immunomodulating agent, failed to protect against poisoning by paracetamol and had no effect on the level of hepatic cytochrome P-450 or the microsomal CCl4-induced lipid peroxidation. This provides a clear connection between the immunostimulating properties of a compound and its effects on xenobiotic biotransformations.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 659-664 
    ISSN: 1432-1041
    Schlagwort(e): BTS 49465 ; hypertension ; pharmacokinetics ; blood pressure effect ; heart rate effect ; side-effects ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic and haemodynamic effects of a 200 mg oral dose of BTS 49465 (7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) were investigated in a double-blind placebo controlled study. BTS 49465 was rapidly absorbed and cleared from the systemic circulation with a half-life of 1.6 h by oxidation to the sulphone metabolite. The metabolite was cleared with a half-life of 37.6 h. Saliva concentrations of both BTS 49465 and its metabolite correlated well with the plasma concentrations. Compared to placebo, BTS 49465 produced statistically significant reductions in blood pressure and increases in heart rate both supine and after a 60° head up tilt. The time course of the haemodynamic changes suggested that the sulphone metabolite contributed to the overall hypotensive response. Plasma Renin Activity was only marginally elevated and there was no evidence of acute fluid retention. BTS 49465 was well tolerated in terms of haematological and biochemical parameters and subjective side-effects.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 447-452 
    ISSN: 1432-1041
    Schlagwort(e): alaproclate ; antipyrine clearance ; serotonin reuptake inhibitor ; healthy volunteers ; antipyrine metabolism ; metabolite clearance ; alaproclate kinetics ; inhibition of drug metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Alaproclate, a selective serotonin reuptake inhibitor, presently undergoing clinical trial for the treatment of major depressive disorders, has been shown to inhibit hexobarbital metabolism in mice. In the present study the influence of oral alaproclate on the total plasma clearance of antipyrine and on the formation of its metabolites was investigated in 10 healthy volunteers. The peak level of alaproclate was reached after about 1.5 h, and after a distribution phase, its plasma elimination half-life was between 3.0 and 3.5 h. Antipyrine tests were performed before treatment, during the first four doses and after the seventh dose of alaproclate 200 mg/day. During treatment, total plasma antipyrine clearance and the clearance for production of all antipyrine metabolites were reduced by 30%, indicating non-selective inhibition of oxidative drug-metabolizing enzyme activity in man by alaproclate. After the last dose of alaproclate, antipyrine plasma clearance and the clearance to its metabolites returned to control values. In order to allow more detailed evaluation of the results, the time course of the clearances for production of metabolites was investigated. This revealed that the extent of inhibition of metabolite formation by alaproclate was dependent on the plasma alaproclate level, indicating a rapidly reversible inhibition.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    ISSN: 1432-1041
    Schlagwort(e): renin ; aldosterone ; dopamine ; natriuretic hormone ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The acute natriuretic effect of human atrial natriuretic peptide (ANP) has been well described in man. We have now studied possible hormonal mediators of this effect. We studied six healthy volunteers on two occasions when they received either an infusion of ANP of 1.5 pmol·kg−1·min−1 for 30 min followed by 15 pmol·kg−1·min−1 for a further 30 min, or matching vehicle infusions in a randomized single-blind fashion. On the placebo day, plasma renin activity (PRA) rose from 1.26±0.08 to 1.57±0.14 ng A1·ml−1·h−1, while on the ANP study day PRA fell from 1.45±0.15 to 1.28±0.05 ng A1·ml−1·h−1 (p〈0.01). No significant changes were found in plasma aldosterone concentrations or in urinary dopamine excretion. These results provide evidence that ANP suppresses renin release in man.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 433-441 
    ISSN: 1432-1041
    Schlagwort(e): antipyrine ; antipyrine metabolites ; drug metabolism ; route of administration ; healthy volunteers ; urinary excretion ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of antipyrine in plasma and saliva, and urinary excretion of its major metabolites, were studied following i.v. and oral administration of antipyrine 500 mg to 6 healthy volunteers. Data from both plasma and saliva showed that the oral bioavailability of antipyrine given as an aqueous solution was complete. The saliva/plasma concentration ratio was constant with time from about 3 h onwards, with a mean value of 0.87 after oral and 0.91 after i.v. administration. It is concluded that the pharmacokinetic parameters of antipyrine can be satisfactorily established on the basis of salivary data, although the volume of distribution and clearance values are then slightly too high. After i.v. administration, 3.8±1.9% of the dose was excreted in urine as unchanged antipyrine in 48h, 24.9±6.3% as 4-hydroxyantipyrine, 16.5±3.2% as norantipyrine, 13.0±2.2% as 3-hydroxymethyl-antipyrine and 5.8±1.0% as 3-carboxy-antipyrine. No significant differences were observed following oral administration. The half-lives calculated from the linear part of the urinary excretion rate curves of the metabolites were about the same for oral and i.v. administration, and were of the same order of magnitude as the elimination half-life of parent drug in plasma and saliva. It is important for determination of the ultimate metabolite ratio that urine is collected for at least 36h, because there is a delay in the excretion of 3-hydroxymethyl-antipyrine in urine.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    ISSN: 1420-9071
    Schlagwort(e): Ethanol ; peroxisomes ; lipid peroxidation ; alcoholic cardiomyopathy ; rat liver ; rat heart
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Chronic ethanol administration was shown to increase catalase and acyl-CoA oxidase activities in rat myocardium but did not alter the activity of liver peroxisomal enzymes. As a result of alcohol consumption a 2–3-fold increase in the level of lipid peroxidation was observed in the heart tissue while in the liver the induction was much less pronounced.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 631-634 
    ISSN: 1432-1041
    Schlagwort(e): salbutamol ; albuterol ; pharmacokinetics ; bioavailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Salbutamol was administered to sixteen healthy male volunteers intravenously and by mouth in liquid, tablet, and capsule form using a Latin-Squares design. Pharmacokinetic parameters from intravenous data were similar to previously reported values obtained with oral administration, with a mean terminal half-life of 3.8 h and a mean clearance of 439 ml·min−1·1.73 m−2. Peak plasma concentrations of 10–20 ng·ml−1 were obtained 1–3 h following oral administration. The absolute bioavailability of each of the oral preparations was 44%. While statistically significant differences in lag time and time to peak concentration were noted among the various oral preparations, the drug is rapidly absorbed in all three dosage forms and the observed differences are unlikely to be of clinical significance.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 151-153 
    ISSN: 1432-1041
    Schlagwort(e): atropine ; bethanechol ; prostigmine ; gallbladder volume ; real-time ultrasonography ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of direct cholinergic stimulation and blockade on gallbladder volume, determined by real-time ultrasonography (RUS), was evaluated in twenty normal, fasting subjects. Eleven subjects received atropine sulphate or placebo and 9 subjects a series of 3 injection of prostigmine, bethanechol or placebo, randomly assigned, at intervals of 24 h. RUS was performed under basal conditions after fasting for 12 h and every 5 min after drug injection up to 45 min in the atropine study and up to 60 min after prostigmine and bethanechol. There was no significant variation from fasting gallbladder volume after placebo in either group. After atropine sulphate gallbladder volume at first decreased and then significantly increased. With bethanechol and prostigmine, the volume fell significantly to a trough after 30 to 35 min, and then it returned to the basal value within 60 min. It is suggested that cholinergic mediation is involved in maintaining fasting tone in the gallbladder and that cholinergic stimulation causes contraction of the gallbladder by a direct effect.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 355-361 
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; smoking ; gender ; pharmacokinetics ; HPLC ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The purpose of this study was to examine the influence of cigarette smoking and gender on the pharmacokinetics of metoprolol. Eighteen volunteers with no evidence of clinical disease each randomly received the following doses of metoprolol tartrate: 100 mg orally, 200 mg orally and 20 mg as a constant-rate intravenous infusion over 20 min. The only significant difference between smokers (S) and nonsmokers (NS) was that S had a larger steady-state volume of distribution (3.3 vs 2.5 l/kg). There were no differences in half-life, systemic clearance or bioavailability (f). No differences were observed between males (M) and females (FM) for any of the kinetic parameters examined. Systemic bioavailability varied markedly between subjects (range: 15 to 92%). In fifteen of the eighteen subjects, f was higher after the 200-mg dose compared to the 100-mg dose. These results suggest that metoprolol may be subject to saturable presystemic elimination and extend the previous observations of Johnsson et al. [1] who showed that f increased from 31% to 46% when doses were increased from 20 to 100 mg. However, the difference in f as the dose is increased is unlikely to be clinically significant since the mean difference is smaller than the variation in f among subjects.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 413-417 
    ISSN: 1432-1041
    Schlagwort(e): antipyrine ; acetaminophen ; lidocaine ; drug interactions ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Pharmacokinetic interactions between antipyrine and acetaminophen were evaluated in 7 healthy volunteers. On 3 occasions subjects received:1, antipyrine 1.0 g intravenously (i.v.);2, acetaminophen 650 mg i.v.;3, antipyrine 1.0 g and acetaminophen 650 mg i.v. simultaneously. Between Trials 1 and 3, antipyrine elimination t1/2 (17.2 vs 17.4 h), clearance (0.44 vs 0.43 ml·min−1·kg−1) and 24-h recovery of antipyrine and metabolites (313 vs 293 mg) did not differ significantly. Between Trials 2 and 3, acetaminophen Vz was reduced (1.14 vs 1.00 l·kg−1), t1/2 prolonged (2.7 vs 3.3 h), clearance reduced (4.8 vs 3.6 ml·min−1·kg−1), and fractional urinary recovery of acetaminophen glucuronide reduced. Eight additional subjects received 50 mg of lidocaine hydrochloride i.v. in the control state, and on a second occasion immediately after antipyrine 1.0 g given i.v. The two trials did not differ significantly in lidocaine Vz (2.6 vs 2.7 l·kg−1), t1/2 (2.0 vs 2.4 h) or clearance (15.0 vs 13.5 ml·min−1·kg−1). Although acetaminophen does not alter antipyrine kinetics, acute administration of antipyrine appears to impair acetaminophen clearance, possibly via inhibition of glucuronide formation. However, antipyrine has no significant effect on the kinetics of a single i.v. dose of lidocaine.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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