Oral absorption of lipidic amino acid conjugates

Abstract A series of unlabelled and radiolabelled lipidic peptide conjugates 2a-2f were synthesised by reduction of 1a-1f with NaBH 4 and NaB 3 H 4 , respectively. Initial in vitro experiments using Caco-2 cell cultures were carried out, to predict the in vivo oral absorption of the conjugates. The optimal lipophilicity for oral uptake was determined following oral administration of compounds 2a-2f to rats. The results suggested that conjugation to lipidic amino acids and peptides is a useful approach to improving the absorption of poorly absorbed drugs. Increasing lipophilicity increased the oral uptake to a certain level, but highly lipophilic compounds showed lower levels of oral uptake.