No abstract

The objective of this study was to determine both the pharmacokinetic parameters and the bioavailability of two commercial 20-mg isosorbide-5-mononitrate (IS-5-MN) preparations (test and reference preparation) after single oral administration. For this purpose, the test and the reference preparation were examined in 24 healthy male volunteers according to a randomized 2-way cross-over design, blood samples were withdrawn up to 24 hours postadministration, and plasma concentrations of IS-5-MN were quantified by a gas chromatography (GC) method. Both preparations led to peak plasma levels of approximately 360 ng/mL IS-5-MN in the mean 0.76 hour (test) and 0.94 hour (reference preparation) after application; the plasma half-lives were about 5.2 hours, and for the areas under the curve (AUC(0-infinity)), mean values of 2741 (test preparation) and 2742 hour.ng/mL (reference preparation) were found. The statistical comparison (analysis of variance, confidence intervals) of the pharmacokinetic parameters found in the study resulted in bioequivalence of both IS-5-MN preparations. The undesired side effects/concomitant symptoms observed are known to occur after IS-5-MN administration.

Synthese und Pharmakologie a mbstituierter Metiamid-AnalogaAus dem Fachbereich Pharmazie der Johannes Gutenberg-Universitat, M a i m und der Pharmakologisch-Toxikologischen Forschung der Fa. Ludwig Heumann u. Co., Numberg". (Eingegangen am 25. Februar 1977) Es wird die Synthese a-substituierter 5(4)-Methyl4 (5)-[ [ 2-(N'-methyl-thioureido)-athylmercapto]methyl]-imidazole 4 aus a-substituierten 4(5)-Methoxymethyl-5(4)-methyl-imidazolen 2 S O W I~ die Hz-antihistaminische Wirksamkeit der dargestellten 4 beschrieben. Hz-Antihistaminics, 11: Synthesis and Pharmacology of a8ubstituted Metiamide Analogues The synthesis of a-substituted 5-methyl-4-(2-[3-( methy1)t hioureido]ethylthiomethyl)-1Himidazoles 4 from &-substituted 4-methoxymethyl-5-methyl-lH-imidazoles 2 is described. The Hz-antihistaminic activity of the products is reported. Nach Black et al.') besitzt N-Methyl-"-[ 2-[(5-methyl-4-imidazolyl)-methylthio]athyl] -thioharnstoff3) (Me tiamid) ausgepragte H2 -antihistaminkche Wirkung. ImRahmen dieser Arbeit interessierte die Beein flussung der pharmakologischen Wirkung bei Substitution an der dem Imidazolring benachbarten Methylengruppe. Daher wurden verschiedene a-aliphatisch und -aromatisch substituierte Analoge dargestell t und vorzugsweise am isolierten spontan schlagenden Vorhof des Meerschweinchens, sowie am Rattenuterus und reperfundierten Rattenmagen untersucht.xymethyl-5(4)-methyl-imidazole in Betracht. Nachdem es uns gelungen war, 2-sub-Als Schliisselsubstanzen fir die Synthese von 4 kamen a-substituierte 4(5)Hydro-

Die Imidazol‐carbinole (I) setzen sich mit den Mercaptanen (II) zu den Thioethern (III) um, aus denen mit den Isocyanaten bzw. Isothiocyanaten (IV) die Metiamid‐Analoga (V) synthetisiert werden.