Pharmacokinetics of a New Analgesic on the Basis of Hexaazaisowurtzitane Derivative.

We studied pharmacokinetics of a new analgesic based on a hexaazaisowurtzitane derivative (thiowurtzine, TWZ). A method for measuring TWZ in organs and tissues by HPLC/MS/MS was developed and validated. The sensitivity of the method under conditions of intragastric administration of TWZ to rats in a dose of 100 mg/kg is 0.5 ng/ml (calibration curve 0.5-400 ng/ml). The concentrations of the substance (Cmax) in the plasma, organs, and tissues of animals were 20-100 ng/ml, the time to reach the maximum concentration after a single dose (Tmax) was 2 h. The mean retention time of the substance in the body ranged from 5.67 to 17.15 h after administration. The highest concentrations were found in excretory organs (liver and kidneys), the substance also actively penetrated into muscle tissue. The medium concentrations were found in the brain and adipose tissue. The tropism to the heart tissues was minimal.

Hepatic and cerebral energy production system in rats with acute and chronic ethanol intoxication.

We studied the effects of ethanol on the energy production system in the brain and liver in acute and chronic intoxications. Ethanol was found to inhibit mitochondrial respiratory chain in the liver. Acute ethanol intoxication results in uncoupling of oxidative phosphorylation. NAD-dependent respiration prevails in chronic intoxication. In the brain, ethanol exposure induces a compensated low-energy shift with activation of fast mitochondrial metabolic cluster and uncoupling of oxidative phosphorylation.