ABSORPTION OF AN OXYTOCIN ANTAGONIST (ANTOCIN) AND A VASOPRESSIN ANALOG (DDAVP) THROUGH A STANDARDIZED SKIN EROSION IN VOLUNTEERS

Purpose. Transdermal administration of the peptides [Mpa(1), D-Tyr (Et hyl)(2), Thr(4), Orn(8)]-oxytocin (antocin) and [Mpa(1), D-Arg(8)]-vas opressin (dDAVP) was studied in healthy volunteers, Methods. A standar dized skin erosion was formed preliminary by suctioning. The peptides were administered in plastic reservoirs through a 5 mm erosion and the absorption was followed for a six-day period with plasma concentratio n determinations on days 1, 3 and 6 with refilling the reservoirs dail y with 15 mu m and 19 mu M solutions of dDAVP and antocin, respectivel y. Fourteen healthy non-smoking volunteers divided equally between the sexes, participated in the study. Plasma concentrations were measured using specific radioimmunoassays. Reservoir concentrations and metabo lic stability of the peptides were determined using reverse-phase HPLC . Results. Both antocin and dDAVP were absorbed across the skin erosio n. The absorption pattern was biphasic with a high initial absorption during days 1 and 2 followed by a lower absorption on days 3 and 6. Th e absorption on day 1, which was estimated at more than 50% for both p eptides during a 24 h period, corresponded to a simultaneous decrease in peptide concentration in the reservoirs. The extent of absorption f or antocin on days 3 and 6 was 1/3 to 1/6, respectively, of that obser ved on day 1. Antocin was minimally degraded in the skin reservoir whi le dDAVP was intact. However, accumulation of cellular material appear ed in the antocin reservoirs. The absorption of antocin was reduced by exposure to intact skin surrounding the skin erosion. No pain was exp erienced and no scar formation was observed. Conclusions. The observed biphasic absorption may be a consequence of the mild inflammatory res ponse occurring subsequent to eroding the skin. The standardized skin erosion may provide a route for the short-term delivery of otherwise p oorly absorbable peptide and protein drugs.