The pharmacokinetics of intraduodenally administered diazepam in rats as influenced by composition of the central lymph.

Abstract

Diazepam, a drug with hydrophobic properties, was used as a model for studying its distribution (after intraduodenal administration) into the central lymph of rats. The intestinal lymph, which prevails in the central lymph, was modified for the presence of total lipids (chylomicrons) by means of fasting, a normal or an artificial diet (olive oil). The lymphatic levels of diazepam exceeded the corresponding blood levels in the fed and oil-fed group; the levels were steady in the fasted group with the exception of the absorption phase of the curves. The kinetic parameters assessed in the blood and lymph of the individual groups obtained by mathematical evaluation of the concentration curves differed because of quantitative differences in the presence of chylomicrons in the lymph. Lymphatic bioavailability in comparison with i.v. administration was found to be substantially lower.