DRUG-DELIVERY STUDIES IN CACO-2 MONOLAYERS .3. INTESTINAL TRANSPORT OF VARIOUS VASOPRESSIN ANALOGS IN THE PRESENCE OF LYSOPHOSPHATIDYLCHOLINE

The transport of a series of vasopressin and oxytocin analogues with v arying lipophilicities was studied in Caco-2 monolayers. Transport was studied across the bare monolayer and after treatment with a phosphol ipid absorption enhancer, palmitoyl lysophosphatidylcholine. The range in lipophilicity of the analogues, estimated as the capacity factor, was found to be from 0.19 to 3.43. The intrinsic transport of the pept ides across Caco-2 monolayers was found to be low. The apparent permea bility coefficients, P-app were in the range of 2 x 10(-8)-6 x 10(-7) cm/s. However, peptide transport was significantly greater (P-app in t he range of 5 x 10(-6)-2 x 10(-5) cm/s) when facilitated by addition o f palmitoyllysaphosphatidylcholine. The results suggest that polypepti de transport across Caco-2 monolayers does not depend on lipophilicity , but that the facilitated transport does depend on the lipophilicity.