Pharmacokinetic Properties of a New Glutamic Acid Derivative Glutaron.

Inhomogenous distribution of glutaron in organs and tissues was found after intravenous and peroral administration: the agent demonstrated high affinity to organs with high degree of vascularization (lungs and heart) and elimination (kidney). Glutaron easily penetrates through the blood-brain barrier, which is consistent with its concentration in the adipose tissue.

[ABSOLUTE AND RELATIVE BIOAVAILABILITY OF GLUTARON--A NEW DERIVATIVE OF GLUTAMIC ACID].

The pharmacokinetics of studies of 3-phenylglutamic acid hydrochloride (glutaron) has been studied in rats. The main pharmacokinetic parameters show low values of the half-life (T1/2 = 3.75 h), mean retention time in the body (MRT = 5.77 h). The medium rate of drug concentration decrease in the blood plasma leads to a low value of the area under pharmacokinetic curve (AUC = 41.18 mg · h/mL). The general volume of distribution (Vd = 3.42 L/kg) is 3.5 times greater than the volume of extracellular fluid in the rat body. These data indicate a high ability of the glutaron to be distributed and accumulated in animal tissues. The value of absolute bioavailability is 84%, and the relative bioavailabity is 100%.

GABA derivatives citrocard and salifen reduce the intensity of experimental gestosis.

Substitution of drinking water with 1.8 % NaCl solution in pregnant female rats from day 1 of gestation until parturitions was followed by the development of experimental gestosis. Gestosis manifested in an increase in BP by 18.2 %, protein concentration in the urine by 6.2 times, and edema severity in muscles, brain, and omentum in comparison with the initial level. The concentration of homocysteine in blood plasma of rats with complicated pregnancy 4.4-fold surpassed that in pregnant rats without gestosis, which can probably in a cause for gestosis development. GABA derivatives citrocard (50 mg/kg) and salifen (15 mg/kg), and the reference substance sulodexide (30 U/kg) reduced the severity of gestosis manifestations, which was seen from the absence of BP rise, decrease in urinary protein concentration by 1.9, 2.0, and 1.3 times and blood level of homocysteine by 1.7, 1.5, and 2.6 times, respectively, and a decrease in edema degree in comparison with female rats with experimental gestosis receiving physiological saline.

Study of the absolute bioavailability of citrocard, a new GABA derivative.

The main pharmacokinetic parameters attest to short elimination half-life and mean retention time of a single citrocard molecule. The average rate of plasma concentration decrease of the compound determined small area under the pharmacokinetic curve. Steady-state distribution volume was low and only slightly surpassed the volume of extracellular body fluids in rat, which indicated moderate capacity of citrocard to distribution and accumulation in the tissues, which is seen from low systemic clearance (Cl) despite the quick elimination of the compound. Absolute bioavailability was 64%.

[Hepatoduodenal circulation and excretion of the new GABA derivative citrocard].

Pharmacokinetic investigation of a new gamma-aminobutyric acid (GABA) derivative cirtocard showed that, upon the intravenous introduction, the drug is determined in high concentrations in organs of elimination--the liver and kidneys. The tissue accessibility amounts to 1.341 for the liver and 4.053 for the kidneys and the separation factor is 1.041 for the liver and 4.486 for the kidneys. The study of drug excretion showed that cirtocard is determined in the urine for 48 h, its nephritic clearance being 0.047 L/h and extra-nephritic clearance, 0.33 L/h. For the unchanged substance, a large significance ofhepatoduodenal circulation is low probable, since no more than 1 - 2% of the introduced dose was isolated with bile over entire experiment. It is established that the removal of the unchanged substance does not exceed 10% of the introduced dose. There is high probability of hepatoduodenal circulation and excretion of the preparation in the form of metabolites.

[Absolute bioavailability of the adenine derivative VMA-99-82 possessing antiviral activity].

Investigation of the main pharmacokinetic parameters of adenine derivative VMA-99-82 in rats showed large values of the half-life (T1/2 = 11.03 h) and the mean retention time of drug molecules in the organism (MRT = 9.53 h). A high rate of the drug concentration decrease in the plasma determines a small value of the area under the pharmacokinetic curve (AUC = 74.96 mg h/ml). The total distribution volume (V(d) = 10.61 l/kg) is 15.8 times greater than the volume of extracellular fluid in the body of rat, which is indicative of a high ability of VMA-99-82 to be distributed and accumulated in the organs and tissues. The absolute bioavailability of VMA-99-82 is 66%.

[Effect of new derivatives of natural nitrogen-containing compounds on the level and metabolism of biogenic amines in brain structures and the life span of rats].

Effects of the analogs of transmitter amino acids on the level of biogenic amines and their metabolism in various structures of brain and on the life span of rats have been studied.