The plasma-lymphatic distribution of ribonuclease (RNase), superoxide dismutase (SODase), and catalase (CTase) modified by monomethoxy (polyethylene glycol) (mPEG) was studied in rats. The lymphatic bioavailability (Fl) of individual enzymes administered intravenously was determined on the basis of plasmatic and lymphatic concentration curves. It was concluded that Fl values depend on enzyme-adduct molecular weight (m.w.). The highest Fl value was found in mPEG-RNase (the lowest m.w.), medium value in mPEG-SODase (intermediate m.w.), and the lowest one in mPEG-CTase (the highest m.w.). The binding of these enzymes in the lymphatic tissue of iliac, intestinal, brachial and neck nodes was also proportional to their molecular weight. The lymphatic binding was dependent on the node localization, higher concentrations being found in the iliac and neck nodes in contrast to the other nodes (intestinal, brachial).
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