Arzneimittel Forsch
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Arzneimittel Forsch · May 1998
Effects of a standardized mistletoe preparation on metastatic B16 melanoma colonization in murine lungs.
The immune response-modifying drug Lektinol is a mistletoe preparation which is standardized with respect to bioactive viscum album agglutinin, the most active component of mistletoe. The present study was designed to evaluate the antimetastatic effects of this preparation following intravenous injection of B16 melanoma cells into mice. The standardized mistletoe extract was administered intravenously in doses of 100, 1000 or 5000 microliters/kg (equivalent to 3, 30 or 150 ng/kg of viscum album agglutinin) once daily for three weeks. ⋯ The percentages of double-positive immature CD4+8+ thymocytes were significantly increased in animals treated with the standardized mistletoe extract. There were no signs of treatment-related toxicity. The results of this study indicate that the standardized mistletoe extract shows antimetastatic activity against B16 melanoma lung colonization.
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Arzneimittel Forsch · Apr 1998
Pharmacokinetics, protein binding and metabolic profile of 3H-icometasone enbutate following intravenous, oral and intratracheal administrations to Sprague-Dawley rats.
Absorption, distribution and excretion of 3H-icometasone enbutate (9 alpha-chloro-11 beta,17 alpha,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione, 17-butyrate, 21-acetate, CAS 103466-73-5 CL09) were studied in male and female Sprague-Dawley rats after a single dose administration by intravenous (1 mg/kg), oral and intratracheal (2 mg/kg) routes. The metabolic profile after the different routes and protein binding were also determined. Independent of the route, the radioactivity was mainly excreted in faeces. ⋯ This binding was demonstrated to be reversible. CL09 was extensively metabolized since no unchanged CL09 was recovered in bile or urine and at least nine metabolites have been detected. The profiles seemed to be different according to the route of administration.
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Arzneimittel Forsch · Aug 1997
Role of caffeine in combined analgesic drugs from the point of view of experimental pharmacology.
The interactions of caffeine (CAS 58-08-2) with acetylsalicylic acid (CAS 50-78-2, ASA) and paracetamol (CAS 103-90-2) were investigated with regard to the analgesic, antiphlogistic, antipyretic and other properties. The inhibitory effect of paracetamol and ASA on the prostaglandin biosynthesis in a cyclooxygenase preparation from bovine brain in vitro was not affected by the addition of caffeine. Caffeine additively increases the antinociceptive effect of paracetamol with regard to the heat-induced pain in the mouse, as does aminophenazone. ⋯ The protective effect of ASA against the hepatotoxic effect of paracetamol in the mouse is not influenced by the addition of caffeine. The plasma levels after the oral administration of 20 mg/caffeine/ kg and 80 mg paracetamol/kg in the rat are not significantly changed when the substances are given in combination. The toxicological advantages resulting from combining ASA and paracetamol with caffeine are discussed.
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Arzneimittel Forsch · Jul 1997
Randomized Controlled Trial Clinical TrialStudies on psychomotoric effects and pharmacokinetic interactions of the new calcium sensitizing drug levosimendan and ethanol.
Levosimendan (CAS 141505-33-1) is a calcium sensitizing drug intended for the treatment of congestive heart failure. In animal experiments levosimendan has potentiated the sedative effects of ethanol. Due to poor water solubility of the compound, ethanol is used as a diluent in the intravenous formulation. ⋯ Levosimendan did neither affect elimination of ethanol. Levosimendan did not potentiate the psychomotoric effects of ethanol neither did it have any psychomotoric effects itself. In conclusion, levosimendan is not likely to have any psychomotoric adverse effects or any clinically significant interactions with ethanol.
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Arzneimittel Forsch · Jun 1997
Randomized Controlled Trial Comparative Study Clinical TrialPlasma profiles of transdermal 17 beta-estradiol delivered by two different matrix patches. A four-way cross-over study in postmenopausal women.
The aim of this study was to investigate the systemic bioavailability and plasma profiles of 17 beta-estradiol (CAS 50-28-2, E2) after the application of two types of matrix patches for the transdermal delivery of E2: MenorestTM (the test patch) with delivery rates of 37.5, 50 and 75 micrograms E2/day and a reference patch with a delivery rate of 50 micrograms E2/day. All 3 test patches were identical in composition, achieving different transdermal E2 delivery rates by variations in the surface area (11.0, 14.5 and 22.5 cm2). All 4 patches were each worn by 24 postmenopausal women over a 4-day period (i.e. 96 h), each of the 4 treatment periods being separated by a 7-day wash-out period according to a randomized, 4-way crossover design. ⋯ However, in the evening, periodically higher E2 plasma levels were observed for all patches than in the morning. From these results it can be concluded that E2 plasma profiles produced by the test patch are reproducible, and in the physiological range consistent with the early to mid follicular level in the premenopausal woman over 4 days (96 h), correlating with the doses administered (37.5-50-75 micrograms E2/d). Additionally, the systemic bioavailability of the test patch at a dose of 37.5 micrograms E2/d is comparable to that of the reference patch at a dose of 50 micrograms E2/d.