[Comparative study of the effect of paracetamol, phenacetin and amidopyrine on mitochondrial function in isolated rat hepatocytes]. / Sravnitel'noe izuchenie deistviia paratsetamola, fenatsetina i amidopurina na funktsiiu mitokhondrii v izolirovannykh gepatotsitakh krys.

Effects of amidopyrine, phenacetin and paracetamol on the viability and energetic state of isolated rat hepatocytes were compared. During incubation in minimal salt solution all drugs in concentrations above 1 mM in dose-dependent manner decreased the viability of hepatocyte suspension assessed by trypan blue dye inclusion and inhibited the ATP synthesis and the respiratory activity. Cytotoxic effect of chemicals decrease in the order: amidopyrine-->phenacetin-->paracetamol. The inhibition of the rate of endogenous respiration were accompanied by stimulation of oxygen consumption in nonmitochondrial systems. An uncoupler of oxidative phosphorylation, 2,4-dinitrophenol, and disruption of plasma membrane by digitonin followed by substrate succinate addition did not restore the respiratory activity of hepatocytes up to the level of control cells. These data show that cytotoxicity of the chemicals is determined by their interaction with enzymes of mitochondrial respiratory chain.

[The effect of paracetamol and its combinations with acetylsalicylic and ascorbic acids on lipid peroxidation processes in the rat liver]. / Vliianie paratsetamola, ego kombinatsii s atsetilsalitsilovoi i askorbinovoi kislotami na protsessy perekisnogo okisleniia lipidov v pecheni krys.

Paracetamolum (PC) after i.p. administration to rats at the therapeutic (100.0 mg/kg) and subtoxic (500.0 mg/kg) doses was shown to induce significant and dose-dependent elevation of the level of malone dialdehyde (MDA) as well as the increase in a certain extent of chemiluminescence (CL) being injected at the higher dose. Acetylsalicylic acid (ASA) at the same doses being injected at the lower one, induced the tendency toward the reduction of MDA level, while at the higher dose the rise of MDA content and CL intensity compared to PC have been observed. PC combination with ASA at therapeutic doses range (50.0 + 50.0 mg/kg) significantly diminished MDA formation, while at subtoxic doses range (250.0 + 250.0 mg/kg) such effect was not detected, although subsequent tendency toward CL intensity reduction was observed. Ascorbinic acid being administered in combination with PC and ASA had no influence on MDA formation but significantly weakened CL intensity when subtoxic doses of indicated drugs were used.

[Analgesic action and pharmacokinetics of lysine acetylsalicylate administered intramuscularly]. / Anal'geticheskoe deistvie i farmakokinetika lizina atsetilsalitsilata pri vnutrimyshechnom vvedenii.

The analgesic effect, acute toxicity and pharmacokinetics of lysine acetylsalicylate (LAS), a water-soluble salt of acetylsalicylic acid (ASA) were studied as compared with a 50% solution of analgin and a 4% solution of amidopyrine at intramuscular administration and ASA administered intragastrically. During inflammation-induced pain in rats LAS exerts a pronounced analgesic effect exceeding the activity of other agents. LD50 of LAS was similar to that of analgin and ASA. LAS toxicity was significantly less than that of amidopyrine. Bioavailability of ASA at intramuscular administration to rabbits was close to that at intravenous injection and significantly higher as compared with intragastric administration.

[Antiaggregation action and pharmacokinetics of lysine acetylsalicylate]. / Antiagregatsionnoe deistvie i farmakokinetika atsetilsalitsilata lizina.

Lysine acetylsalicylate, a water-soluble salt of acetylsalicylic acid, administered intravenously to rabbits (15 and 100 mg/kg) and also in vitro (2-10 mg/ml) produced antiaggregational and anticoagulant effects pertaining to acetylsalicylic acid. Pharmacokinetics of acetylsalicylic acid injected intravenously to rabbits in the form of lysine acetylsalicylate is formalized by a biexponential equation for a two-compartment model. The main pharmacokinetic constants of acetylsalicylic acid in these experiments were found to be similar to those in humans.