High performance liquid chromatographic determination of Picumast and two active metabolites in plasma using on-line sample preparation.

A method for determining Picumast, an antiallergic drug, in plasma by HPLC and column switching has been developed. The system consisted of two precolumns, an analytical column, three pumps, an autosampler and a fluorescence detector. The precolumns (17 x 4.

Solid-phase extraction and liquid chromatography of torsemide and metabolites from plasma and urine.

Torsemide is a new diuretic drug with a profile of action similar to that of furosemide. The high potency of torsemide results in low dose therapy and causes problems for the pharmacokinetic study of the drug due to low plasma levels. Described here are methods for the analysis of torsemide and two metabolites in plasma and urine using solid-phase extraction and liquid chromatography.

Pharmacokinetics of picumast dihydrochloride in patients with liver cirrhosis.

In a randomized parallel group design the pharmacokinetics of picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarine++ + dihydrochloride) and its active metabolites M1 and M2 were studied after intravenous or oral administration of a single dose of 10 mg picumast dihydrochloride in two groups of 8 patients with liver cirrhosis. After intravenous administration, the terminal half-life of 65 h was about 4 times longer than in healthy subjects although the total body clearance of 87 ml/min was only 7.4% lower.

Study of potential kinetic interactions of picumast dihydrochloride and theophylline in vitro and after oral administration in man.

The kinetic interaction of picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin dihydrochloride) and theophylline has been studied in vitro (displacement from protein binding) and in vivo in healthy male non-smokers after oral administration. In a randomized, three-way cross-over study, 12 subjects received at weekly intervals either separated or combined single doses of picumast dihydrochloride (10 mg) and theophylline (7 mg/kg b.w.

Pharmacokinetics of picumast dihydrochloride and its active metabolites M1 and M2 in humans.

The pharmacokinetics of picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin dihydrochloride) and the pharmacodynamically active metabolites M1 and M2 as well as the absolute bioavailability of picumast dihydrochloride have been studied in healthy volunteers after oral administration of the drug in doses which were considerably higher than therapeutically used. After intravenous administration of 10 mg picumast dihydrochloride a peak concentration of 182 ng/ml was achieved at the end of the 1 h infusion. Picumast dihydrochloride was extensively distributed to the tissues (Vz = 130 l) and almost exclusively eliminated by hepatic metabolism (total clearance 95 ml/min, amount of unchanged compound excreted in urine below detection limit).

Pharmacokinetics of picumast after administration of 14C-picumast dihydrochloride in dogs, rats, rabbits and monkeys.

In dogs, rats, monkeys and rabbits, picumast (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin ) is eliminated from the plasma by metabolic clearance. Its main metabolic pathway is oxidation of the 3-methyl group of the coumarin ring. After oral administration, the parent compound accounted for less than 15% of the concentration of radioactivity in the plasma.

Metabolism of picumast after administration of picumast dihydrochloride and antiallergic activity of the main metabolites.

The present experiments were carried out to elucidate the chemical structure and the pharmacological activity of the main metabolites of picumast (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin ). The metabolic pathways were identical in animals and man, but there were major quantitative differences. The fraction of the radioactivity in the plasma attributable to the parent compound 0.

Pharmacokinetics and metabolism of torasemide in man.

Torasemide (1-isopropyl-3-([4-(3-methyl-phenylamino)pyridine]-3- sulfonyl)urea) is a potent new loop diuretic. The pharmacokinetics, absolute bioavailability and metabolic disposition of torasemide have been studied after administration of a standard-release tablet to healthy volunteers. According to a latin square design 9 subjects received in random order single doses of either 20 mg i.

Pharmacokinetics of the thioether phospholipid analogue BM 41.440 in rats.

BM 41.440 (1-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine) is a cytotoxic thioether phospholipid analogue that recently has entered phase I trials in cancer patients. The objective of this study was to evaluate the pharmacokinetics of this compound in female rats after administration of a single oral dose (15 mg/kg body weight [bw] ).

The determination of torasemide and metabolites in plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of torasemide and two active metabolites is described. The assay uses a reversed-phase gradient system and UV-detection. Sample preparation includes deproteinisation and liquid-solid extraction incorporating an internal standard.

Quinidine-digoxin interaction: evidence for involvement of an extrarenal mechanism.

The influence of quinidine 750mg per day for one week on serum digoxin concentration (SDC) was evaluated in digitalized anuric patients on chronic haemodialysis. During quinidine administration the SDC increased markedly, from 0.84 +/- 0.

[Investigation of the viability of radioactively labelled bacteria after adsorption on activated charcoal (author's transl)].

A method for radioactive labelling of bacteria is described. [35S]-L-methionine labelled Staphylococcus aureus and Escherichia coli used as model microorganisms were adsorbed onto the surface of acrylhydrogel coated charcoal. On the average 33% of S.

Enzymatic inhibition assay for fluorometric determination of allopurinol and oxipurinol in serum and urine.

An enzymatic inhibition assay for the xanthine oxidase (XOD) inhibitors allopurinol and oxipurinol is described. 2-Amino-4-hydroxypteridine is used as sensitive fluorogenic substrate, which is oxidized to highly fluorescent isoxanthopterin by XOD. Increasing concentrations of allopurinol (Ap) or oxipurinol (Ox) prevent conversion of 2-amino-4-hydroxypterdine to isoxanthopterin.

Clinical and pharmacological investigations of the new saluretic azosemid.

Ple 1053 (Azosemid) is a diuretic which resembles furosemide chemically and in its mode of action. When administered intravenously, Ple 1053 was approximately 5 times more potent on a weight basis than furosemide, its dose-response relationship was closer and the slope was steeper. After oral administration Ple 1053 and furosemide were approximately equal in potency.

On the bound state of alkali cations in subcellular preparations of rat liver.

Gel filtration and ion-specific electrodes were used together with atomic absorption spectrophotometry in a search for substances in rat liver which are capable of binding alkali cations. In the cytosol, a material which binds K specifically and reduces the ion activity of potassium can be detected. The binding material, which may be destroyed by alpha-chymotrypsin, has been purified about 100-fold.