The pharmacokinetics of intravenously administered diazepam in the rat influenced by composition of the lymph.
Diazepam, a drug with hydrophobic properties, was used as a model drug for the study of its distribution after i.v. administration into the central lymph of the rat. The intestinal lymph, which prevails in the central lymph, was modified for the presence of total lipids chylomicrons by fasting and a normal or an artificial diet (olive oil). Lymphatic levels of diazepam in all three experimental conditions exceeded the corresponding blood levels, being lowest in the fasted group, higher in the normally fed animals and highest in the oil-fed group. Experimental blood and lymphatic data were subjected to pharmacokinetic analysis. The changes in the parameters were found to depend quantitatively upon the presence of chylomicrons in the lymph. Lymphatic availability of diazepam in the central lymph is stimulated by an increased content of the chylomicrons fraction of the lymph.
Lamka
J
J
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Hradec Králové.
Jindrová
O
O
Rudisar
L
L
Gallová
S
S
Kvĕtina
J
J
D000818:Animals; D002914:Chylomicrons / Q000032:analysis; D003975:Diazepam / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D005215:Fasting; D007275:Injections, Intravenous; D008055:Lipids / Q000032:analysis*; D008196:Lymph / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis
D002914:Chylomicrons; D004042:Dietary Fats, Unsaturated; D008055:Lipids; D003975:Diazepam