Pharmacokinetics and metabolism of ryodipine in rats.

2,6-Dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1, 4-dihydropyridine (ryodipine, PP-1466) at oral administration in the form of a suspension with Tween (polysorbate) 80 addition is comparatively rapidly absorbed in the gastro-intestinal tract and circulates in blood for a long period of time. PP-1466 practically does not bind to plasma proteins. The drug is mainly excreted via the kidneys and with faeces by 49 and 46% of the dose administered after 96 h, respectively. PP-1466 metabolites are present in rat urine-2,6-dimethyl-4-arylpyridine-3,5-dicarbonic acid derivatives: oxidation product of PP-1466 dihydropyridine cycle into pyridine one, products of partial or complete hydrolysis of ester groups of PP-1466 oxidized form, lactones. There have been performed the synthesis of labelled 14C-PP-1466 as well as counter-synthesis of PP-1466 metabolites. Unchanged PP-1466 is not detected in urine.

[Effect of silicoorganic compounds on protein biosynthesis in granulation-fibrous tissue]. / Vliianie kremniiorganicheskikh soedinenii na biosintez belkov v granuliatsionno-fibroznoi tkani.

The authors studied the effect of propoxysilatran (POS) on the biosynthesis of the main connective tissue biopolymeres. The use of POS in the form of 0.5 and 2.0% ointments on lanolin-vaseline base caused stimulation of cellular proliferation in the granulation fibrous tissue developing in the open skin defects of albino rats. Stimulation of cellular proliferation in these animals was accompanied by increase of collagen biosynthesis and of noncollagen proteins. In concentrations of 10(-3)--10(-4) M POS caused intensification of collagen biosynthesis (formation of peptide-bound nondialyzed 14C-oxyproline) in vitro in the cartilage tissue of chick embryos. Thus, silatrans are biologically-active substances producing a regulating effect on the course of the reparative-proliferative processes in the connective tissue.

[Demethylation of methindione]. / Demetilirovanie metindiona.

Methindion demethylation was shown to occur in rats. This process proceeds with the participation of NADPH-dependent transport system of microsomal electrons. In experiments in vivo methindion demethylation coursed at a high rate and was accompanied by a partial loss of its anticonvulsive effects.

[Interaction of 2,6-dimethyl-3,5-dicarbethoxy-1,4-dihydropyridine with enzymes of the NADP.H2-specific electron transport chain of rat liver microsomes]. / Vzaimodeistvie 2,6-dimetil-3,5-dikarbetoksi-1,4-digidropiridina s fermentami NADF.H2-spetsifichnoi tsepi perenosa élektronov mikrosom pecheni krys.

2,6-Dimethyl-3,5-dicarboethoxy-1,4-dihydropyridine (DHP) interacts with NADPH-dependent electron transfer system of rat liver microsomes: it forms a complex with the terminal oxidase-cytochrome P-450, according to type I, and inhibits clearly the activity of NADPH-cytochromes c-reductase and mitindione dimethylesterase. DHP repeatedly administered in vivo rendered no inducing influence upon the microsomal enzymes.

[Pharmacokinetics of ftorafur-2-14C in rats with Walker carcinosarcoma]. / Farmakokinetika ftorafura-2-14C u krys s kartsinosarkomoi Uokera.

The pharmacokinetics of phthorafur-2-14C (Ph) was investigated after its intravenous injection to rats with Walker carcinosarcoma. The blood plasma level of Ph-2-14C and its metabolites proved to decrease in to a three-phase process. The content of the agent in the tissues decreased in the following sequence: the kidney, small intestine, tumour, stomach, muscle, heart, liver, lungs, spleen, brain and fat. The tumour was observed to contain Ph-2-14C and endogenous metabolite 5-phthoruracil-2-14C. Excretion of the agent continued for 48 hrs, 52.2% of the administered dose being eliminated via the urinary tract, 30% as 14CO2, and 0.8% in feces.

[Participation of non-specific rat liver microsome oxidases in destruction of Nl-furanidylpyrimidines]. / Uchastie nespetsificheskikh oksidaz mikrosom pecheni krys v razrushenii Nl-furanidilpirimidinov

N1-(3'-Butyrolactono)-5-fluorouracil, N1-(2'-furanidyl) 5-trifluoromethyluracil, N1-(2'-furanidyl)-5-fluoracil are split in the rat organism with the formation of free 5-fluorouracil. The destruction of the C--N bonds in the molecule of the N1-(2'-furanidyl)-5-fluoracil takes place in the liver microsomes. This process is strengthened by NADPH and weakened by SKF-525A. All the three furanidylpyrimidines studied induced differential spectra of type I in the suspension of the liver microsomes. This fact testifies to the interaction of these substances with the cytochrome P-450.

[Clinical pharmacokinetics of 2-C14-ftorafur in patients with astrocytoma]. / Klinicheskaia farmakokinetika 2-C14-ftorafura u bol'nykh astrotsitomoi

Patients with dedifferentiated brain astrocytoma during an operation were injected intravenously 2-C14-fluorofur (3 muC/Kg). In different periods after the injection the level of radioactivity was determined in different sites of the tumor, brain tissue, as well as in blood plasma, cerebrospinal liquor and urine. Intracellular localization of the labeled substance in the tumor tissue was examined autohistoradiographically. 2-C14-fluorofur was found to readily penetrate the hemato-encephalic barrier and to be absorbed both by tissues of neuroectodermal tumor and adjacent brain tissues. In astrocytoma cells the labelled substance is localized mainly extranuclearly. Radioactive products are excreted from the organism slowly and their traces are observed in blood, cerebrospinal liquor and urine even on the third day postoperatively.

[Pharmacokinetics of dioxonium]. / Farmakokinetika dioksoniia

An investigation in the pharmacokinetics of a new peripheral muscle relaxant dioxonium and of its carbon-labeled analogue (with respect to the N-methyl groups) was carried out. An intravenous administration of dioxonium-C14 was found to bring about a biphasic change in radioactivity of the blood plasma. The stoppage of curarization, irrespective of a dioxonium dose, is seen to occur at a definite radioactivity level in the blood plasma. Major radioactivity following introduction of dioxonium-C14 is observed in the organism of the rats in the skeletal muscles and in the kidneys. The drug is eliminated from the organism through the kidneys in an unchanged and pharmacologically active form.