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  • 1
    ISSN: 1432-1041
    Keywords: urapidil ; left ventricular failure ; haemodynamic parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Urapidil, a new alpha1-adrenoceptor blocking drug, has been shown to be effective in the treatment of hypertension. Ten normotensive patients with severe congestive heart failure were given Urapidil 25 mg i.v. twice in 15 min and the haemodynamic effects were measured. There was a significant fall in systolic blood pressure (−16%), mean blood pressure (−13%), left ventricular end-diastolic pressure (−38%), mean pulmonary artery pressure (−31%) and wedge pressure (−40%). Total peripheral resistance fell by 25%, whereas pulmonary arteriolar resistance did not change significantly. Cardiac output increased by 22%. The increase in cardiac output with decreasing peripheral resistance and LV pressures suggests that urapidil may be useful in the therapy of congestive heart failure.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: urapidil ; digoxin ; blood drug level ; pharmacokinetics ; drug absorption/-interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open, randomized, two-period change-over study the effect of urapidil, an antihypertensive agent, on steady-state serum digoxin levels was investgated in 12 healthy male volunteers. The subjects were given digoxin 0.25 mg once daily for 4 days to produce a steady-state digoxin level in serum. At the end of that time the subjects received either digoxin monotherapy or digoxin and concomitant treatment with urapidil 60 mg b.d. for a further 4 days. Subsequently the treatments were changed over. The absorption characteristics Cmax and tmax of digoxin were not altered by concomitant urapidil treatment. The geometric mean and nonparametric 95% confidence limits of digoxin relative bioavailability were 97% (93%–103%). Therefore, concomitant administration of urapidil with digoxin treatments did not appear to alter the rate and extent of absorption of the glycoside.
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  • 3
    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.
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  • 4
    ISSN: 1432-0843
    Keywords: Dexniguldipine-HCl ; Phase I trial ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dexniguldipine-HCl is a new dihydropyridine compound that exerts selective antiproliferative activity in a variety of tumor models and, in addition, has a high potency in overcoming multidrug resistance. The purpose of this trial was to determine the toxicity and pharmacokinetics of dexniguldipine and to establish a recommended dose for phase II trials. A total of 37 patients with cancer were treated with oral dexniguldipine in increasing doses for up to 7 days. The main parameters evaluated were subjective tolerance and laboratory and cardiovascular parameters (blood pressure and ECG). Blood samples were drawn for analysis of the drug's pharmacokinetics. Dizziness and nausea were the major adverse events observed in seven patients, but episodes were generally mild and not clearly dose-related. Vomiting occurred in one patient. Hypotensive effects and orthostatic dysregulation were observed in some patients but were not considered to be dose-limiting. Therefore, no dose-limiting toxicity was found and the maximally tolerable dose could not be determined. Pharmacokinetic data showed wide interindividual variation and a dose-dependent increase in steady-state serum concentrations at doses of up to 1,000 mg daily, with no clear further increase being observed at higher doses. Consistently high concentrations were achieved with the 2,500-mg dose. Despite the lack of dose-limiting toxicity, higher doses of dexniguldipine do not appear to be useful for clinical evaluation because of the pharmacokinetics properties of the compound; therefore, 2,500 mg/day is recommended as the daily dose for phase II trials.
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  • 5
    ISSN: 1432-0843
    Keywords: Key words Dexniguldipine-HCl ; Phase I trial ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Dexniguldipine-HCl is a new dihydropyridine compound that exerts selective antiproliferative activity in a variety of tumor models and, in addition, has a high potency in overcoming multidrug resistance. The purpose of this trial was to determine the toxicity and pharmacokinetics of dexniguldipine and to establish a recommended dose for phase II trials. A total of 37 patients with cancer were treated with oral dexniguldipine in increasing doses for up to 7 days. The main parameters evaluated were subjective tolerance and laboratory and cardiovascular parameters (blood pressure and ECG). Blood samples were drawn for analysis of the drug’s pharmacokinetics. Dizziness and nausea were the major adverse events observed in seven patients, but episodes were generally mild and not clearly dose-related. Vomiting occurred in one patient. Hypotensive effects and orthostatic dysregulation were observed in some patients but were not considered to be dose-limiting. Therefore, no dose-limiting toxicity was found and the maximally tolerable dose could not be determined. Pharmacokinetic data showed wide interindividual variation and a dose-dependent increase in steady-state serum concentrations at doses of up to 1,000 mg daily, with no clear further increase being observed at higher doses. Consistently high concentrations were achieved with the 2,500-mg dose. Despite the lack of dose-limiting toxicity, higher doses of dexniguldipine do not appear to be useful for clinical evaluation because of the pharmacokinetic properties of the compound; therefore, 2,500 mg/day is recommended as the daily dose for phase II trials.
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  • 6
    ISSN: 1432-1777
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Repetitive DNA sequences form a substantial portion of eukaryotic genomes and exist as members of families that differ in copy number, length, and sequence. Various functions, including chromosomal integrity, gene regulation, and gene rearrangement have been ascribed to repetitive DNA. Although there is evidence that some repetitive sequences may participate in gene regulation, little is known about how their own expression may be regulated. During the course of gene trapping experiments with embryonic stem (ES) cells, we identified a novel class of expressed repetitive sequences in the mouse, using 5′ rapid amplification of cDNA ends-polymerase chain reaction (5′ RACE-PCR) to clone fusion transcripts from these lines. The expression of these repeats was induced by retinoic acid (RA) in cultured ES cells examined by Northern blot analyses. In vivo, their expression was spatially restricted in embryos and in the adult brain as determined by RNA in situ hybridization. We designated this family of sequences as Dr (developmentally regulated) repeats. The members of the Dr family, identified by cDNA cloning and through database search, are highly similar in sequence and show peculiar structural features. Our results suggest the expression of Dr-containing transcripts may be part of an ES cell differentiation program triggered by RA.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Infection 7 (1979), S. 187-189 
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Der 4-Stunden-Urin von freiwilligen Versuchspersonen und Patienten, die oral oder intravenös Penicilline erhalten hatten, wurde dünnschichtchromatographisch und mit Hilfe der Bioautographie untersucht. Bei nur zwei von 12 Penicillinen — Amoxicillin und Mezlocillin — waren keine antibakteriell aktiven Metaboliten nachzuweisen. Bei den übrigen Penicillinen besaßen diese unterschiedliche antibakterielle Aktivität, wie bei Verwendung verschiedener Testmikroorganismen gezeigt werden konnte. Nach Gabe von Carbenicillinestern wurden drei anti-bakteriell aktive Flecken getrennt, einer von ihnen entsprach dem Penicillin G; die beiden anderen besaßen Aktivität gegenüberPseudomonas aeruginosa. Das Bioautogramm nach Azlocillin-Therapie zeigte zwei Komponenten mit Aktivität gegenüberBacillus subtilis, Staphylococcus aureus undEscherichia coli; gegenüberP. aeruginosa jedoch war nur der schnell wandernde Fleck aktiv. Über die Bildung und die chemische Beschaffenheit dieser zusätzlichen aktiven Komponenten besteht noch weitgehend Unklarheit. Es ist jedoch durchaus möglich, daß sie die Bioverfügbarkeit eines Antibiotikums beeinträchtigen.
    Notes: Summary Four-hourly urine from volunteers and patients who had received penicillins orally or intravenously was investigated by means of thin layer chromatography and bioautography. Antibacterially active metabolites were not detected with only two of 12 penicillins, namely amoxicillin and mezlocillin. In the case of the other penicillins the metabolites possessed variable antibacterial activity as could be demonstrated using different test microorganisms. After administration of carbenicillin esters three antibacterially active spots were detected, one of which corresponded to penicillin G; the other two were active againstPseudomonas aeruginosa. The bioautogram after treatment with azlocillin showed two components which were active againstBacillus subtilis, Staphylococcus aureus andEscherichia coli; only the rapid moving component was active againstP. aeruginosa, however. The formation and chemical nature of these additional active components is still to a large extent not understood. It is quite possible, however, that they affect the bio-availability of an antibiotic.
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