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  • Articles  (49)
  • Articles: DFG German National Licenses  (49)
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  • Articles  (49)
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  • Articles: DFG German National Licenses  (49)
  • Latest Papers from Table of Contents or Articles in Press
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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and absolute bioavailability of salbutamol in healthy adult volunteers (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 631-634 
    Details
    ISSN: 1432-1041
    Keywords: salbutamol ; albuterol ; pharmacokinetics ; bioavailability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02456001
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of cholinergic agonists and antagonists on gallbladder volume in fasting man (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 151-153 
    Details
    ISSN: 1432-1041
    Keywords: atropine ; bethanechol ; prostigmine ; gallbladder volume ; real-time ultrasonography ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544559
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  • 3
    Electronic Resource
    Electronic Resource
    Absorption of an aqueous solution of a new synthetic somatostatin analogue administered to man by gavage (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 167-171 
    Details
    ISSN: 1432-1041
    Keywords: somatostatin analogue ; oral formulation ; gastrointestinal absorption ; SMS 201-995 ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To determine the local gastrointestinal absorption of a new synthetic somatostatin analogue (SMS 201-995 = Sandostatin), an intestinal tube was passed in eight healthy volunteers and on different days an aqueous solution was administered at four different locations: stomach, proximal duodenum, ligament of Treitz and jejunum. In a follow-up study, an oro-ileal tube was passed in six of the original volunteers and the drug solution was administered in to the terminal ileum. The aqueous solution of SMS was rapidly absorbed from the gastrointestinal tract after local application, and it was well tolerated. Absorption of the drug from the different sites was comparable, although there was a tendency to decreased peptide absorption after ileal administration. Absorption of the drug was quite variable between the subjects and the different locations. The dose-corrected systemic availability relative to subcutaneous administration in another study was 0.28%. However, significant plasma SMS concentrations were achieved, suggesting that oral delivery of the polypeptide may eventually be possible for long-term treatment of a variety of disorders.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544562
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  • 4
    Electronic Resource
    Electronic Resource
    Enoxacin — a potent inhibitor of theophylline metabolism (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 227-230 
    Details
    ISSN: 1432-1041
    Keywords: enoxacin ; theophylline ; drug interaction ; healthy volunteers ; adverse effects ; pharmacokinetics ; renal tubular excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The mechanism of the theophylline-enoxacin interaction has been studied in six healthy subjects. Theophylline 250 mg was administered p.o., twice daily for 11 days in a sustained release dosage form. On the 4th day of treatment, blood samples were taken every 2 h and urine was collected over 1 dose interval. From Days 5 to 11 coated tablets of enoxacin 400 mg b.i.d. were coadministered. On Day 11 blood and urine were collected as on Day 4. The mean plasma theophylline concentration rose from 4.4 to 15.1 mg/l, corresponding to a 73.6% reduction in total clearance. The urinary excretion of unchanged theophylline increased from 12.7 to 35.3%, whereas the production of metabolites was reduced (1-demethylation 81.4%; 3-demethylation 83.1%, 8-hydroxylation 74.6%). The results indicate that the theophylline-enoxacin interaction may be due to inhibition of the cytochrome P-450 isozymes responsible for theophylline metabolism. Unexpectedly, the renal clearance of theophylline metabolites was found to be drastically reduced when enoxacin was coadministered. This led to unchanged or even to elevated plasma levels of the metabolites. The mechanism of this interaction is still to be elucidated, but it may be due to competition for renal tubular secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637553
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  • 5
    Electronic Resource
    Electronic Resource
    Effect of 6-hourly intermittent intravenous boluses of oxmetidine and ranitidine on gastric acidity and serum prolactin (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 267-271 
    Details
    ISSN: 1432-1041
    Keywords: ranitidine ; oxmetidine ; gastric acidity ; bolus injection ; serum prolactin ; healthy volunteers ; gastric pH ; gastric juice volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect on 24-h gastric juice volume and pH of 30 min intravenous infusions of 200 and 400 mg oxmetidine and 50 mg ranitidine, administered at 6-hourly intervals, has been investigated in 12 healthy male subjects. After each infusion period a median intragastric pH 〉5 was obtained with all active treatments, which also caused a significantly elevated 24-h median pH versus placebo. The 24-h median pH following ranitidine did not differ significantly from that after either oxmetidine treatment. There was a sharp decrease in gastric volume secretion within 2 h of infusion of each active treatment. There was no significant difference between active treatments in the time required to reach an intragastric pH 〉5. No active treatment was able to maintain the pH 〉5 for longer than 4 h (average 3 h). It is concluded that in patients at risk of stress ulcer, continuous infusion therapy with H2-blockers should be employed both for pharmacokinetic and practical reasons. It should be accompanied by regular measurement of pH in order to monitor any fall in pH. Alternatively, shorter time intervals than 6 h should be used for bolus therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637560
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  • 6
    Electronic Resource
    Electronic Resource
    Influence of smoking and gender on the disposition kinetics of metoprolol (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 355-361 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; smoking ; gender ; pharmacokinetics ; HPLC ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637630
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  • 7
    Electronic Resource
    Electronic Resource
    Effect of 40749 RP on basal and sham feeding stimulated gastric secretion in man (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 479-482 
    Details
    ISSN: 1432-1041
    Keywords: 40749 RP ; gastric acid secretion ; gastric antisecretory agent ; sham feeding ; healthy volunteers ; vagal stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 40749 RP, a pyridyl-2-tetrahydrothiophene derivative, is known to be a potent inhibitor of the gastric acid response to pentagastrin, betazole and a meal. In 6 healthy young volunteers, a single oral dose of 2 mg · kg−1 greatly reduced the gastric acid secretory response to sham-feeding. By contrast, neither gastric pepsin nor the plasma PP response were altered by the drug. No change was observed in plasma gastrin, motilin, VIP or somatostatin concentrations. The results show that 40749 RP is also active on the pure vagus-stimulated gastric acid secretion. The lack of effect upon gastric pepsin and plasma PP suggests that 40749 RP is not likely to act on the basolateral cholinergic receptor and that it affects further cellular steps involved in hydrogen ion secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544239
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  • 8
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of indoramin and 6-hydroxyindoramin in poor and extensive hydroxylators of debrisoquine (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 59-65 
    Details
    ISSN: 1432-1041
    Keywords: indoramin ; 6-hydroxyindoramin ; debrisoquine ; hydroxylators ; genetic polymorphism ; blood pressure ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five poor metabolisers (PM) and seven extensive metabolisers (EM), of debrisoquine, all healthy volunteers, received 50 mg indoramin orally following an overnight fast. Plasma concentrations of indoramin and 6-hydroxyindoramin were determined by HPLC with fluorimetric detection. In PM subjects, mean values of Cmax (158 ng/ml) and AUC(0–24) (2556 ng·h·m−1) for indoramin were substantially elevated and t1/2β (18.5 h) prolonged by comparison with values in the EM subjects (21.6 ng/ml, 151 ng·h·ml−1 and 5.2 h respectively). For 6-hydroxyindoramin, on the other hand, Cmax (12.4 ng/ml) and AUC(0–8) (47.5 ng·h·ml−1) in PM subjects were significantly lower than in the EM subjects (28.2 ng/ml and 94.7 ng·h·ml−1). There was a tendency to a higher incidence of side-effects in the PM group. Although the difference did not achieve statistical significance (0.1〉p〉0.05), all the PM subjects experienced sedation compared to only two in the EM group. Differences in blood pressure and pulse rate between the two groups were small. It is concluded that the oxidative metabolism of indoramin is subject to genetic polymorphism, which is probably under the control of the same gene locus as that influencing debrisoquine oxidation. The clinical consequences are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610381
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  • 9
    Electronic Resource
    Electronic Resource
    Psychomotor, respiratory and neuroendocrinological effects of buprenorphine and amitriptyline in healthy volunteers (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 139-146 
    Details
    ISSN: 1432-1041
    Keywords: buprenorphine ; amitriptyline ; interaction ; psychomotor performance ; respiration ; pituitary hormones ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Actions and interactions of buprenorphine (BUP) and amitriptyline (AMI) on performance and respiration were studied double-blind and cross-over in 12 healthy volunteers. After one-week pretreatments with AMI or placebo, the subjects received on Day 8 placebo, BUP or AMI so that the final treatments were 1) placebo, 2) acute AMI 50 mg, 3) acute BUP, 4) subchronic AMI + acute BUP and 5) subchronic AMI. The subacute treatments were started at two-week intervals. A Mapleson D rebreathing circuit including a pneumotachograph and an infrared capnograph was employed to study drug effects on respiration. Minute volume and end-tidal carbon dioxide as well as psychomotor performance were measured and the blood samples taken on Day 8 before the drug intake and 2 and 4 h thereafter. The performance tests included tracking, choice reaction, flicker fusion, exophoria, nystagmus, digit symbol substitution and the subjective assessment of mood. BUP depressed respiration, and subchronic AMI increased this depression. Both BUP and acute AMI 50 mg each alone impaired various measures of performance and rendered the subjects drowsy, feeble, mentally slow and muzzy but subchronic AMI did not enhance BUP effects. BUP increased plasma prolactin levels similarly after both pretreatments. The results suggest that both BUP and AMI moderately affect psychomotor performance but the interaction between these agents is mild and restricted mainly to respiration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544557
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  • 10
    Electronic Resource
    Electronic Resource
    Inhibition of pentagastrin-stimulated gastric acid secretion and plasma levels of the new histamine H2-receptor antagonist ramixotidine dihydrochloride (CM 57755) in human volunteers (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 467-470 
    Details
    ISSN: 1432-1041
    Keywords: ramixotidine ; cimetidine ; CM 57755 ; H2-receptor antagonist ; gastric acid secretion ; healthy volunteers ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The new competitive histamine H2-receptor antagonist, ramixotidine 2 HCl (CM 57755), has been tested in healthy male volunteers for its ability to inhibit pentagastrin-stimulated gastric acid secretion. In the first study, in 8 subjects, pentagastrin 6 µg·kg−1 was injected s.c., 90 min after the following 4 oral treatments given in random order at weekly intervals: placebo, 100, 200 and 400 mg CM 57755. Gastric contents were collected over 15-min periods during the 2 h after pentagastrin stimulation. In a second, similar study, 8 subjects received placebo, 0.5 and 1.0 g CM 57755 and 800 mg cimetidine, 120 min before a 2 h i.v. infusion of 6 µg·kg−1·h−1 pentagastrin. Cumulative gastric secretion in placebo-treated subjects was 46±14 and 62±11 mmol H+·2 h−1 (mean±SD), respectively, in the first and second studies. It was significantly reduced only after 400 mg CM 57755 in the first study. In the second study either dose of CM 57755 and cimetidine caused a significant reduction in gastric acid secretion. Average plasma levels of ramixotidine were dose-related after 0.2 and 1.0 g and ranged from 0.3 and 1.6 µg/ml, respectively, at 60 min to 0.5 and 3.7 µg/ml at 180 min. The peak cimetidine level averaged 3.6 µg/ml at 150 min. Individual CM 57755 plasma levels throughout the test period were fairly consistent with the inhibition of cumulative gastric acid secretion scored concurrently in each subject. No subjective side-effects attributable to the treatments were reported, and no abnormal findings were seen in the ECG or in laboratory tests.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637671
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