Arzneimittel Forsch
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Arzneimittel Forsch · Apr 1994
Absorption, distribution, metabolism and excretion of [14C]ebastine after a single administration in rats.
Absorption, distribution, metabolism and excretion of ebastine (4'-tert-butyl-4-[4-(diphenylmethoxy)piperidino]butyrophenone, LAS-90, CAS 90729-43-4), a novel antihistamine, were investigated with 14C-labeled compound in rats after a single oral or intravenous administration, in comparison with [14C]carebastine, an active metabolite of ebastine. After intravenous administration of [14C]ebastine at 2 mg/kg, the plasma level of radioactivity decreased biphasically with alpha-phase half-life (t1/2 alpha) of 1.6 h and beta-phase half-life (t1/2 beta) of 3.1 h. After administration of [14C]carebastine, a similar plasma level-time profile was observed with t1/2 alpha of 0.7 h and t1/2 beta of 2.1 h. ⋯ Similar results were observed after oral administration at 0.2, 2 and 20 mg/kg. Following administration of [14C]carebastine, the recovery of radioactivity in urine and feces were around 2% and 96% of the dose, respectively, irrespective of administration route. In the plasma 2 h after oral administration of [14C] ebastine, carebastine and the polar metabolite(s) were observed as major components, whereas ebastine was hardly detected.(ABSTRACT TRUNCATED AT 400 WORDS)
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Arzneimittel Forsch · Jan 1994
Effect of vintoperol on platelet aggregation and experimental thrombosis.
The platelet aggregation inhibitory and antithrombotic effect of the new peripheral circulation enhancing compound vintoperol (RGH-2981, CAS 106498-99-1) was studied. In vitro, vintoperol inhibited the aggregation response to collagen in platelet-rich plasma from mice, rats, rabbits and dogs. It was found to be highly effective in preventing mice from acute pulmonary thromboembolic death induced by adenosine diphosphate (ADP) or collagen. ⋯ In mice receiving 30 mg/kg vintoperol orally, the inhibition of aggregation response to collagen, ADP and ADP/epinephrine by 15, 33 and 37%, respectively, was associated with a substantial increase in bleeding time. In a rat multifactorial thrombosis model the 10 mg/kg p.o. dose was also sufficient to obtain significant antithrombotic effect (p < 0.01). Results of these experiments indicate that vintoperol interferes with platelet aggregation both in vitro and in vivo and possesses potent antithrombotic effects in thrombosis models in which platelet activation is mainly involved.
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Arzneimittel Forsch · Dec 1993
Comparative StudyComparative pharmacokinetics of oral dextromethorphan and dextrorphan in the rabbit.
The pharmacokinetics of dextromethorphan (CAS 125-71-3) and its metabolite dextrorphan (CAS 125-73-5) was compared. The drugs were administered orally at the same molar dose of 0.085 mmol/kg. ⋯ The concentrations of 3-hydroxymorphinan were higher after dextromethorphan than dextrorphan. 3-Methoxymorphinan was detectable only 60 and 120 min after dextromethorphan. This work proposes the therapeutic use of dextrorphan instead of its precursor dextromethorphan.
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Arzneimittel Forsch · Dec 1993
DNA single strand breaks in peripheral human lymphocytes after anesthesia with isoflurane-nitrous oxide-oxygen.
DNA single strand breaks were determined in peripheral lymphocytes of neurosurgical patients before and after 180 min of general anesthesia with isoflurane (CAS 26675-46-7)-nitrous oxide-oxygen. Immediately after anesthesia, the frequency of DNA single strand-breaks appeared to be significantly enhanced. In the majority of patients the DNA single strand breaks induced was equivalent to the effect of 0.2-0.5 Gray following x-ray radiation of lymphocytes in vitro. ⋯ Then an increase of the frequency of DNA single strand breaks could not be demonstrated any more. The DNA single strand breaks were repaired by cellular repair systems. As DNA repair is regulated genetically, isoflurane-nitrous oxide-oxygen could induce DNA damage in patients with DNA repair defects.
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Arzneimittel Forsch · Dec 1993
Comparative StudyDisposition of the novel anticancer agent vinorelbine ditartrate following intravenous administration in mice, rats and dogs.
1. KW-2307 (vinorelbine ditartrate, CAS71486-22-1) is a new semisynthetic antitumour vinca alkaloid. Its pharmacokinetics, distribution and excretion were investigated following intravenous administration to mice (1.2 mg/kg), rats (0.12 and 1.2 mg/kg) and dogs (0.4 mg/kg). ⋯ The tissue distribution profile of radioactivity in rats was similar after single and repeated administrations. 5. Radioactivity was excreted mainly in faeces (61-73% dose in 48 h and 71-79% dose in 168 h). Biliary excretion accounted for 42.6% dose in rats during 48 h although enterohepatic cycling was probably unimportant.