Male Wistar rats were maintained on a nutritionally adequate diet and diazepam was administered in a dose of 10 mg/kg/day. Control animals were pair-fed an adequate diet. Feeding was continued for 180 days, and the effects on the liver, plasma and erythrocyte phospholipid content were studied. It was found that the contents of sphingophospholipids and phosphatidylinositol + phosphatidylserine were significantly reduced in the erythrocytes of diazepam-treated rats. There was a significantly increased content of phosphatidylcholine in the liver and erythrocytes after 180 days of diazepam treatment. Such treatment did not cause statistically significant changes in the plasma of diazepam-treated rats. These investigations are in agreement with the hypothesis that extended or chronic use of drugs such as diazepam may alter membrane-dependent processes.
The lymphatic bioavailability (FL) of diazepam (DZ) and its major metabolite desmethyldiazepam (DDZ) was studied. DZ was administered in intravenous and intraduodenal boluses, and in intravenous infusion in three groups of rats with different total lipid (TL) content in the central lymph. The effect of a) different lipophilicity of DZ and DDZ, b) lymphatic TL content, and c) route of DZ administration on Fl was determined. It was found that a) FL values of DZ exceeded the Fl values of DDZ and b) Fl values of DZ increased with increasing TL content in the lymph (an opposite relation was found in DDZ), and c) the highest Fl value of DZ + DDZ sum after intravenous
The effects of chronic diazepam treatment (10 mg/kg/day for 180 days) on the fractional distribution and fatty acid composition of heart phospholipids were studied in male Wistar rats. It was found that diazepam treatment increased the content of phosphatidylcholine and cardiolipin in the heart and slightly increased its phosphatidylcholine fraction. There were no significant changes in fatty acid composition after diazepam treatment in heart phospholipids, with the exception of significant decrease of 20:3n-6 and 20:5n-3 fatty acids. Our findings suggest that diazepam, probably through peripheral benzodiazepine binding sites, altered the content of heart cardiolipin and caused changes in the flux of oxidative phosphorylation in the heart.