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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 4 (1987), S. 251-254 
    ISSN: 1573-904X
    Schlagwort(e): amiodarone ; antipyrine ; desethylamiodarone ; drug metabolism ; drug interactions ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The effect of amiodarone on hepatic drug metabolism in vivo was examined in the rat using antipyrine as a model substrate. Pretreatment with oral amiodarone hydrochloride, 100 mg/kg/day, for 5 days resulted in a 19% reduction in antipyrine clearance and a 22% increase in half-life. The administration of single oral doses of amiodarone hydrochloride, 100 mg/kg, 1 or 5 hr prior to antipyrine administration had no significant effect on antipyrine pharmacokinetics. The administration of a single intravenous dose of amiodarone hydrochloride, 50 mg/kg, reduced antipyrine clearance by 32% and increased the half-life by 46%. The desethyl metabolite of amiodarone was also found to reduce antipyrine clearance (21%) after a single oral dose of 100 mg/kg.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 6 (1989), S. 477-480 
    ISSN: 1573-904X
    Schlagwort(e): acetylation ; immunomodulators ; interferon inducers ; pharmacokinetics ; procainamide ; tilorone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Interferon and interferon inducers have been found to inhibit cytochrome P-450-dependent metabolism in animals and man. The effect of these agents on the acetylation of drugs has not been previously reported. Since these agents stimulate the reticuloendothelial system, together with the abundance of N-acetyltransferase in the reticuloendothelial system, it was hypothesized that these immunomodulators may affect drug acetylation. To test this hypothesis, the effect of tilorone (a synthetic interferon inducer) on the in vivo acetylation of procainamide was examined in the rat. Pretreatment with tilorone hydrochloride (50 mg/kg) 48 hr prior to the administration of procainamide hydrochloride (50 mg/kg) resulted in a 32% increase in the urinary recovery of N-acetylprocainamide and a 35% increase in the metabolic clearance of procainamide to N-acetylprocainamide. These data indicate that interferon inducers increase the N-acetylation of drugs in vivo.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 4 (1987), S. 515-518 
    ISSN: 1573-904X
    Schlagwort(e): antipyrine ; drug metabolism ; hydralazine ; hypothermia ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The concomitant administration of hydralazine with metoprolol or propranolol substantially increases the oral bioavailability of these beta-blockers, presumably via reduction of the first-pass effect. It has been suggested that this effect may be secondary to a decrease in the intrinsic clearance of propranolol, possibly by inhibition of oxidative metabolism. To examine the possibility that hydralazine alters oxidative metabolism in vivo, the effect of hydralazine on the pharmacokinetics of antipyrine was examined in the rat. The oral administration of hydralazine hydrochloride, 7.5 mg/kg, 15 min prior to antipyrine administration reduced antipyrine clearance from 9.66 ± 1.18 to 8.19 ± 0.76 ml/min/kg (P 〈 0.05). Hydralazine was observed to cause substantial hypothermia. The study was repeated in temperature-regulated animals and no alteration in antipyrine clearance was found. Two doses of hydralazine in temperature-regulated rats also failed to alter antipyrine clearance. Thus, it appears that the effect of hydralazine on antipyrine clearance is secondary to the hypothermic effect of hydralazine and not due to a direct inhibition of cytochrome P-450-mediated enzyme activity.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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