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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Cardiovascular drug reviews 8 (1990), S. 0 
    ISSN: 1527-3466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Cardiovascular drug reviews 14 (1996), S. 0 
    ISSN: 1527-3466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Cardiovascular drug reviews 11 (1993), S. 0 
    ISSN: 1527-3466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Cardiovascular drug reviews 15 (1997), S. 0 
    ISSN: 1527-3466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1437-1596
    Keywords: Scalp hair ; Fluoroquinolone ; Q-35 ; Index of exposure ; Time marker ; Kopfhaare ; Fluorochinolon ; Q-35 ; Aufnahme-Indikator ; Zeitmarker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung Kopfhaarproben wurden über einen Zeitraum von 3 Monaten monatlich von gesunden männlichen freiwilligen Versuchspersonen erhalten, welche in Verbindung mit einer Phase I-Studie ein neues antimikrobielles Fluorochinolon-Derivat (Q-35) erhalten hatten. Die Haare wurden sukzessive in 1 cm lange Stücke zerschnitten. Korrespondierende Teile von insgesamt 5 Haarsträngen wurden in 1M NaOH gelöst und mittels einer HPLC-Methode auf Q-35 untersucht. Die Verbindung war erkennbar in den Haaren aller Versuchspersonen nachzuweisen, welche entweder eine einzelne (400 mg,n = 6) oder wiederholte orale Dosen von Q-35 (400 mg/Tag für 6,5 Tage, insgesamt 2.600 mg,n = 6) erhalten hatten. Die Haarabschnitte, welche die Substanz enthielten, erwiesen sich bei den meisten Versuchspersonen als auswärts wandernde Haarschäfte, welche entsprechend zur Haarwuchsgeschwindigkeit ungefähr 1 cm pro Monat nach außen wuchsen. Q-35 (600 mg/Tag) wurde auch 6 gesunden männlichen freiwilligen Probanden für die Dauer von 6,5 Tagen gegeben (insgesamt 3.900 mg) und Haarproben über einen Zeitraum von 1–3 Monaten nach der Gabe gesammelt. Wurde Q-35 entlang eines einzelnen Haarschaftes analysiert, war die Substanz nur in 1-2 konsekutiven, 1 cm langen Stücken detektierbar; auch diese zeigten eine Auswärtsbewegung des Haarschafts über die Zeit. Weitergehende Analysen zeigten, daß die Droge nur in 2–4 konsekutiven, 2,5 mm langen Stücken des Haares enthalten war, welches 3 Monate gesammelt worden war; hierdurch wird gezeigt, daß keine bedeutsame zeitabhängige axiale Diffusion der Substanz entlang des Haarschafts stattfindet. Diese Befunde zeigen die Anwendbarkeit dieses Fluorochinolon-Derivats in menschlichen Kopfhaarproben als Index für eine Substanzaufnahme und als Zeitmarker für die Analyse anderer Drogen im Haar an.
    Notes: Summary Scalp hair samples were obtained every month for three months after administration from healthy male volunteers who participated in the phase I study of a new antimicrobial fluoroquinolone derivative (Q-35). Hairs were cut into 1 cm long pieces successively from the scalp end. Corresponding pieces of 5 hair strands were dissolved in 1M NaOH and assessed for Q-35 by HPLC. The drug was detectable in the hairs of all subjects taking either a single (400 mg,n = 6) or repeated oral doses of Q-35 (400 mg/day for 6.5 days, total 2600 mg,n = 6). The hair portions containing the drug were shown in most subjects to move outwards along the hair shafts month by month in proportion to the hair growth rate of about 1 cm/month. Q35 (600 mg/day) was also given to 6 healthy male volunteers for 6.5 days (total 3900 mg) and hair samples were obtained 1 and 3 months after administration. When Q-35 was analyzed along a single hair shaft, the drug was detectable only in 1–2 consecutive 1 cm long pieces, which were also shown to move outwards along the hair shaft with time. A detailed analysis revealed that the drug was contained only in 2–4 consecutive 2.5 mm long pieces of a single hair collected after 3 months, showing that there was no significant axial diffusion of the drug along the hair shaft with time. These findings indicate the utility of measuring this fluoroquinolone derivative in human scalp hair as an index of drug exposure and as a time marker for analyzing other drug(s) in hair.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 342 (1990), S. 683-690 
    ISSN: 1432-1912
    Keywords: Bepridil ; Lidocaine ; Intraventricular conduction ; ST-T alternans ; Myocardial ischaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Effects of bepridil, an antiarrhythmic and antianginal drug, on intraventricular conduction in acutely ischaemic and infarcted myocardium were examined in anaesthetized dogs, and compared with those of lidocaine. Bepridil at doses of 2 and 5 mg/kg markedly prolonged the conduction time of a premature excitation induced by a ventricular stimulation in the infarcted zone. The effect of bepridil was dependent on a coupling time of the stimulation. Bepridil showed a marked effect at a coupling time of 150 ms, while it showed no significant effect at a prolonged coupling time of 1 s. In other words, the effect of bepridil was interval-dependent. Lidocaine showed a similar interval-dependent effect, but the effect of lidocaine at a longer coupling time was less than that of bepridil. The premature stimulation produced severely delayed conduction which resulted in reentrant beats. Bepridil blocked these conductions, thereby preventing reentrant beats. In contrast to the depressant effect of bepridil in the infarcted myocardium, bepridil prevented the prolongation of conduction time during acute ischaemia. The alternation of the ST-T complex during acute ischaemia which is also an important arrhythmogenic factor was also attenuated by bepridil. Contrary to bepridil, lidocaine significantly enhanced the conduction delay and the alternation in the ST-T complex. In conclusion, bepridil as well as lidocaine showed an interval-dependent depression of the conduction in the infarcted zone of the heart, whereas during acute ischaemia bepridil in contrast to lidocaine attenuated the conduction delay and ST-T alternans.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of infection and chemotherapy 2 (1996), S. 271-279 
    ISSN: 1437-7780
    Keywords: S-1090 ; oral cephem antibiotic ; phase I clinical studies ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract S-1090, an oral cephem antibiotic, was given to healthy male volunteers in single (10 to 400 mg) and multiple (200 mg, twice a day) doses. There were no abnormalities in subjective and objective signs, or physical findings, in any subjects. The intestinal and oropharyngeal bacterial flora were not significantly affected by S-1090. These results suggest that S-1090 is a safe and well-tolerated drug. Food intake increased the absorption of S-1090, but did not affect its half-life. The plasma concentration increased with increasing doses, but at a rate less than proportional to the dose, in the single-dose studies. S-1090 was eliminated with a half-life of 2 to 3 hours after oral administration under nonfasting conditions, independent of dose. Urinary recovery rate decreased with increasing doses. The maximum plasma concentration, half-life, and area under the concentration-time curve at the dose of 100 mg in nonfasting conditions were 3.78 μg/ml, 2.77 hours, and 25.51 μg·h/mL, respectively. S-1090 may be absorbed by both unsaturable passive and saturable active transport systems. During multiple dosing, the extent of absorption decreased slightly, but steady state was achieved within several days without changes in half-life. S-1090 binds to serum protein constantly, at a very high 97%, which might cause the long half-life of this drug. The high plasma concentration and long half-life of S-1090 are favorable for clinical use.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1912
    Keywords: Photochemical reaction ; Thrombosis ; Coronary artery ; Arrhythmia ; Thromboxane A2 synthetase inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During i. v. infusion of rose bengal (48 mg/kg/h), the proximal portion of the rat left coronary artery was illuminated from the outside of the myocardium by green light (540 nm) to produce a transluminal thrombus subsequent to endothelial damages. The primary endothelial damages within the illuminated vascular portion, which resulted from the photochemical reaction between the dye and green light, and the subsequent formation of transluminal platelet-rich thrombus, were easily revealed by both light and electron microscopy. The establishment of the thrombus was accompanied in all cases by the occurrence of ventricular arrhythmias due to myocardial ischaemia. The times required to initiate ventricular premature beats (VPBs) and ventricular tachycardia (VT) were 381 ± 96 s and 444 ± 114 s (mean ± SEM, n = 10), respectively. Pretreatment of the rat with acetylsalicylic acid (3 and 10 mg/kg, i. v.) before the initiation of illumination had no effect on the times required to exhibit the first VPBs and VT, the incidences of both types of arrhythmias were not reduced, and the thrombus was finally formed. On the other hand, pretreatment with Y-20811, a novel thromboxane A2 synthetase inhibitor (0.3, 1 and 3 mg/kg, i. v.), delayed the onset of both VPB and VT in a dose-dependent manner. The incidences of VPBs and VT were significantly reduced at 1 and 3 mg/kg, and the thrombus formation was prevented. The formation of a transluminal thrombus in the left coronary artery by the present technique was highly reproducible and could be functionally evaluated by the occurrence of ventricular arrhythmias.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1912
    Keywords: Fluvoxamine ; Amitriptyline Canine myocardial infarction ; Epicardial activation delay ; Arrhythmia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the effects of fluvoxamine and amitriptyline on epicardial activation delay of premature excitations, the effective refractory period, and the incidence of ventricular arrhythmias by programmed electrical ventricular stimulation in the canine heart after myocardial infarction. Additionally, we investigated whether the inhibition of norepinephrine reuptake by amitriptyline contributes to epicardial activation delay or arrhythmias by combination with propranolol pretreatment. Amitriptyline, at a dose of 3 mg/kg, significantly prolonged epicardial activation delay of premature excitations in the infarcted zone in a frequency-dependent manner (n = 10). Amitriptyline also prolonged epicardial activation delay of premature excitations in the normal zone (n = 10). The effective refractory period in the infarcted zone was significantly prolonged by amitriptyline at a dose of 3 mg/kg (n = 8). Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n = 8). Propranolol did not affect the epicardial activation delay caused by amitriptyline or the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n = 6). Fluvoxamine, on the other hand, had no significant effect on epicardial activation delay of premature excitations (n = 10) or the effective refractory period (n = 8) in both the infarcted and normal zones. Fluvoxamine did not increase the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n = 8). From the present results, fluvoxamine seems to have lower cardiac toxicity than amitriptyline. Moreover, the electrophysiological effects of amitriptyline in this model may be due to a direct cardiac depressive action, but not to the inhibition of norepinephrine reuptake.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1912
    Keywords: Key words Fluvoxamine ; Amitriptyline ; Canine myocardial infarction ; Epicardial activation delay ; Arrhythmia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied the effects of fluvoxamine and amitriptyline on epicardial activation delay of premature excitations, the effective refractory period, and the incidence of ventricular arrhythmias by programmed electrical ventricular stimulation in the canine heart after myocardial infarction. Additionally, we investigated whether the inhibition of norepinephrine reuptake by amitriptyline contributes to epicardial activation delay or arrhythmias by combination with propranolol pretreatment. Amitriptyline, at a dose of 3 mg/kg, significantly prolonged epicardial activation delay of premature excitations in the infarcted zone in a frequency-dependent manner (n=10). Amitriptyline also prolonged epicardial activation delay of premature excitations in the normal zone (n=10). The effective refractory period in the infarcted zone was significantly prolonged by amitriptyline at a dose of 3 mg/kg (n=8). Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n=8). Propranolol did not affect the epicardial activation delay caused by amitriptyline or the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n=6). Fluvoxamine, on the other hand, had no significant effect on epicardial activation delay of premature excitations (n=10) or the effective refractory period (n=8) in both the infarcted and normal zones. Fluvoxamine did not increase the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n=8). From the present results, fluvoxamine seems to have lower cardiac toxicity than amitriptyline. Moreover, the electrophysiological effects of amitriptyline in this model may be due to a direct cardiac depressive action, but not to the inhibition of norepinephrine reuptake.
    Type of Medium: Electronic Resource
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