OBJECTIVE: The enhancement of ascites following intravenous administration of Gd-DTPA on MRI was investigated. MATERIALS AND METHODS: Magnetic resonance imaging was performed in 20 patients with ascites (8 peritoneal carcinomatosis, 2 tuberculous peritonitis, 8 liver cirrhosis, 1 nephrotic syndrome, 1 peritoneal adhesion), and T1-weighted SE images were obtained before and 15-20 min following intravenous administration of Gd-DTPA (0.1 mmol/kg). RESULTS: There were 10 exudative ascites and 10 transudative ascites. Eight of 10 exudative ascites showed enhancement, in contrast to none of 10 transudative ascites. The precontrast signal intensity ratios (SIRs) of exudative ascites were significantly higher (p < 0.05) than those of transudative ascites, and the postcontrast SIRs of exudative ascites were significantly higher (p < 0.01) than those of transudative ascites. This difference was thought to be caused by increased peritoneal permeability and higher protein concentration in the cases with exudative ascites in this study. CONCLUSION: It is concluded that enhancement of ascites on MRI obtained 15-20 min after intravenous administration of Gd-DTPA is not an uncommon finding in exudative ascites (especially associated with peritoneal carcinomatosis).

Ascites↗

PubMedDate not supplied

Studies of metabolic pathways of trimebutine by simultaneous administration of trimebutine and its deuterium-labeled metabolite.

Trimebutine maleate (I), (+-)-2-dimethylamino-2-phenylbutyl 3,4,5-trimethoxybenzoate hydrogen maleate, and a deuterium-labeled sample of its hydrolyzed metabolite, 2-dimethylamino-2-phenylbutanol-d3 (II-d3), were simultaneously administered to experimental animals at an oral dose of 10 or 50 mumol/kg, and distribution ratios of the two alternative initial metabolic steps, i.e., ester hydrolysis and N-demethylation, were estimated by determining the composition of the urinary alcohol-moiety metabolites, II, and its mono- and di-demethylated metabolites, III and IV, by GC/MS. In dogs, the order of quantities of the metabolites from II-d3 was II much greater than III much greater than IV, showing predominance of conjugation over N-demethylation. However, this order was reversed when the amounts of the metabolites from I were compared, indicating that I was preferentially metabolized by N-demethylation followed by ester hydrolysis and conjugation in this order. In rats, a considerable proportion of I was presumed to be metabolized by ester hydrolysis before N-demethylation. In in vitro experiments employing the liver microsomes and homogenates of liver and small intestine from rats and dogs, it was found that both ester-hydrolizing and N-demethylating activities were higher in rats than in dogs, and the conjugating activity was higher in dogs than in rats. It was also found that I, having a high lipophilicity, was more susceptible to N-demethylation than less lipophilic II. These results from the in vitro experiments could account for the species differences in the distribution ratio of the metabolic pathways of I in vivo.

Animals↗

PubMedDate not supplied

In vitro metabolism of the new cardiotonic agent denopamine (TA-064) by rat and rabbit liver preparations. Oxidation, methylation, and glucuronidation.

The metabolic pathways of the cardiotonic agent denopamine, (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol, were studied in vitro with rat and rabbit liver preparations. 4'-O-Demethylated (M-1), 3'-O-demethylated (iso-M-1), and 3-hydroxylated (M-4) metabolites of denopamine were formed by incubation of denopamine with the rat liver microsomal fraction containing the NADPH-generating system. The ratio of M-1 to iso-M-1 formed in this system was 33:1. 3-Methoxydenopamine (M-2) and 3-hydroxy-4-O-methyldenopamine (iso-M-2) were formed via the catechol intermediate M-4, when denopamine was incubated with the rat liver 9000g supernatant fraction in the presence of the NADPH-generating system and S-adenosyl-L-methionine. The ratio of M-2 to iso-M-2 in this system was 7:1. Conversion of iso-M-2 to M-2, i.e. 4-O-demethylation followed by 3-O-methylation, but not vice versa, took place in this system. M-2 was demethylated at 4' to form M-3 by the above microsomal system. M-1 was not ring-hydroxylated by this system, excluding the metabolic route to M-3 via M-1. Denopamine, M-1, M-2, and M-3 were glucuronidated in vitro by the rabbit liver microsomal fraction. The glucuronides of denopamine and M-2 were conjugated at the 4-phenolic hydroxy group, and the glucuronides of M-1 and M-3, which possess two phenolic hydroxy groups, were preferentially conjugated at the 4'-hydroxy group. The order of the rates of in vitro glucuronidation was M-3 greater than M-1 greater than M-2 greater than denopamine.

Animals↗

PubMedDate not supplied

Metabolism of a new cardiotonic agent, (-)-alpha-(3,4-dimethoxyphenethylaminomethyl)-4-hydroxybenzyl alcohol (TA-064), in man. O-demethylation and ring hydroxylation.

A method is described for the determination of plasma concentration of (-)-alpha-(3,4-dimethoxyphenethylaminomethyl)-4-hydroxybenzyl alcohol (TA-064), a new, selectively inotropic cardiotonic agent, based on selected ion monitoring gas chromatography-mass spectrometry. The plasma TA-064 concentration rose rapidly and reached a peak within 60 min after oral administration. The mean peak value of five volunteers was 14.4 ng/ml. About 30-40% of the dose was excreted as free and conjugated TA-064 and conjugates of five metabolites in the human 24-hr urine. The five urinary metabolites were characterized by mass spectrometry after gas- or high performance liquid chromatographic separation: they were 4'-demethyl-, 3-methoxy-, and 4'-demethyl-3-methoxy-TA-064 as the major and 3'-demethyl- and 3-hydroxy-4-methoxy-TA-064 as the minor metabolites. Therefore, the metabolic reactions involved are demethylation at either one of the two adjacent methoxy functions and hydroxylation at the ortho position to the phenolic hydroxy group followed by methylation of either one of the two vicinal hydroxy groups. The ratio of 4'- and 3'-demethyl-TA-064, which of the dimethoxy functions was the one demethylated, was 17:1, and that of 3-methoxy-4-hydroxy- and 3-hydroxy-4-methoxy-TA-064, the phenolic moiety which was vicinally hydroxylated followed by methylation of one of catecholic dihydroxy function, was 6:1.

Adult↗