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 stability of the peptide by protecting it from enzymatic degradation. The enzymatically labile peptides TRH and LHRH were conjugated to lipoamino acids and lipopeptides. The conjugates were labelled on the N-terminal 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 oral administration. In general the uptake of tripeptide TRH analogues was higher than the decapeptide LHRH analogues. Within the same series, conjugates with two lipidic moieties showed higher uptake than the conjugates with one lipidic unit. The novel conjugates developed have been absorbed and detected after oral administration and appear to be stable for a considerable time in vivo.