[Pharmacokinetics of n-(5-oxynicotinoyl)-L-glutamic acid calcium salt upon bolus administration in rats and rabbits: interspecies extrapolation].

The pharmacokinetics of N-(5-oxynicotinoyl)-L-glutamate (ONG) was studied in rats (doses, 20, 100 and 500 mg/kg) and rabbits (50 mg/kg) after bolus administration of calcium salt of N-(5-oxynicotinoyl)-L-glutamic acid (Ampasse preparation). The ONG concentration in the blood serum was determined by HPLC assay with fluorimetric detection. The lower limit of accurate detection for ONG was 100 ng/ml. The ONG pharmacokinetics in rats was linear at relatively small doses (20-100 mg/kg) but nonlinear at a large dose (500 mg/kg). The ONG concentration decay had a two-phase character in both rats and rabbits, so that the pharmacokinetic profiles were fitted to a biexponential equation of the two-compartment model. Systemic pharmacokinetic parameters determined in rats and rabbits, respectively, were as follows: total clearance, 18 and 15 ml/(min kg); steady state distribution volume, 330 and 880 ml/kg; mean retention time, 0.3 and 1.0 h; half-life, 0.73 and 2.3 h. Using the allometric approach to the interspecies extrapolation of the pharmacokinetic data, the half-life of ONG in humans is predicted to be 4 h.

[Estimation of the efficacy of screened natural hypolipidemic compounds in a model of rabbit hypercholesterolemia]. / Otsenka éffektivnosti otobrannykh prirodnykh gipolipidemicheskikh veshchestv na modeli giperkholesterinemii u krolikov.

Thirteen strains producing hydrophobic compounds with high hypolipidemic activity were screened among 657 tested strains of fungi, actinomycetes and bacteria with the use of 2 models. The further aim of the study was to estimate the efficacy of the compounds with respect to their ability to inhibit cholesterol synthesis in vivo. For that purpose a model of hyperlipidemia in rabbits was used. The model provided screening of 9 new compounds that showed satisfactory hypolipidemic effect evident from a significant decrease of the lipid levels in the rabbit serum. The study of the serum lipid profile revealed that the inhibitory effect of compounds No. 16 and No. 281 was similar to that of lovastatin whereas the serum level of general cholesterol remained decreased for a longer period. Compound No. 25 was of interest because of its possible use in low doses and significant effect on the serum triglyceride fraction.

[Effect of methylcobalamin and adenosylcobalamin on the process of hematopoiesis and vitamin B12 exchange in experimental phenylhydrazine-induced anemia in rabbits]. / Vliianie metilkobalamina i adenozilkobalamina na protsessy krovetvoreniia i obmen vitamina B12 pri éksperimental'noi fenilgidrazinovoi anemii u krolikov.

Poisoning of rabbits with phenylhydrazine resulted in development of haemolytic hyperchromic anemia accompanied by impairment of hemopoiesis in bone marrow as well as by an increase of total vitamin B12 content in blood. The ration of individual forms of cobalamins was firstly estimated in blood serum of healthy rabbits and of the animals treated with phenylhydrazine. Distinct decrease in the methyl cobalamin content was observed in blood serum during spontaneous recovery. Administration of methyl cobalamin led to complete normalization of some blood and hematopoiesis patterns, as well as to restoration of total cobalamins content and the spectrum of their individual forms. Adenosyl cobalamin exhibited distinctly lower effect on the patterns studied. The data obtained suggest that methyl cobalamin possessed a lot of advantages in treatment of hemolytic anemias.