ORAL ABSORPTION STUDIES OF LIPIDIC CONJUGATES OF THYROTROPIN-RELEASING-HORMONE (TRH) AND LUTEINIZING-HORMONE-RELEASING HORMONE (LHRH)

The lipoamino acids and their oligomers provide an excellent means of enhancing peptide lipophilicity and also increase the biological stabi lity of the peptide by protecting it from enzymatic degradation. The e nzymatically labile peptides TRH and LHRH were conjugated to lipoamino acids and lipopeptides. The conjugates were labelled on the N-termina l with a [H-3]acetyl group, administered orally to rats and the uptake examined. A high level of radiolabel uptake was observed in the blood , liver, spleen, kidneys, small intestine and large intestine after or al administration. In general the uptake of tripeptide TRH analogues w as higher than the decapeptide LHRH analogues. Within the same series, conjugates with two lipidic moieties showed higher uptake than the co njugates with one lipidic unit. The novel conjugates developed have be en absorbed and detected after oral administration and appear to be st able for a considerable time in vivo.