On the limiting factors affecting the distribution of model drugs from blood into the lymphatic system.
The effect of molecular weight, lymph quality (total lipid content) and pathological conditions (liver cirrhosis, malabsorption state, acute uremia) on the distribution of model drugs into central lymph after i.v. administration was studied in rats. Lymphatic bioavailability (FL), expressing the ratio of the areas under both the lymphatic and the blood concentration curves, served as the parameter of "lymphotropy". In model drugs with a low molecular weight (benzoates, hippurate, diazepam), the blood and lymphatic concentrations are steady (FL values are close to 1.00). Inulin (m.w. = 5600) in small doses (0.75 mg/kg) possesses a FL similar to low-molecular substances; additions of 10-fold and 50-fold doses significantly increase the FL. High--molecular HSA passes into the lymph to a limited degree only (FL = 0.49). The content of lipids in the central lymph determines the magnitude of FL for the lipophilic drug (diazepam) only. The induced pathological conditions affect the absolute values of both the blood lymphatic areas under the concentration curves, but the resultant FL varies only slightly.
Lamka
J
J
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Heyrovskehko, Czechoslovakia.
Rudisar
L
L
Kvetina
J
J
D000818:Animals; D001682:Biological Availability; D001769:Blood / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004032:Diet; D050356:Lipid Metabolism; D008196:Lymph / Q000378:metabolism; D008208:Lymphatic System / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D008970:Molecular Weight; D010599:Pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains