Quantitation and comparison of phenobarbital levels in the plasma, saliva, and cerebrospinal fluid of the rat, and the demonstration of an alteration of drug passage by ethanol.
In this study, the ability and extent of three biological fluids--plasma, saliva, and cerebrospinal fluid--to compartmentalize intravenously administered phenobarbital was examined and correlated. The three fluid compartments show markedly different levels of phenobarbital, though this probably does not reflect qualitative differences in the barriers that separate them, but rather in the nature of the compartments themselves. In addition to the quantitation and correlation of drug levels in the various compartments, intravenous administration of 400 mg/kg ethanol following the intravenous administration of 20 mg/kg phenobarbital was shown to alter the passage of phenobarbital into the different fluid compartments, causing a significant increase in the phenobarbital level of cerebrospinal fluid as compared to controls receiving no ethanol. Though the effect seen in the cerebrospinal fluid is significant, while the effect in saliva is not (though the trend was present), it is felt that the action of ethanol to alter drug passage is a non-specific effect on the vasculature. This finding of altered drug passage may help explain the observed synergistic interaction of ethanol and various sedative drugs.
D000818:Animals; D002463:Cell Membrane Permeability; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D050356:Lipid Metabolism; D008297:Male; D010634:Phenobarbital / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D012463:Saliva / Q000032:analysis*; D012995:Solubility; D013997:Time Factors
D000431:Ethanol; D010634:Phenobarbital