OXPRENOLOL ABSORPTION IN MAN AFTER SINGLE BOLUS DOSING INTO 2 SEGMENTS OF THE COLON COMPARED WITH THAT AFTER ORAL DOSING

The systemic availability of oxprenolol [a .beta.-adrenoceptor antagonist] after colonic and oral administration was compared in a crossover study involving 6 healthy male volunteers. Drug administration into 2 regions of the colon (cecum and left flexure) was achieved by means of a colonoscopic technique. There were no obvious differences in plasma concentrations after drug administration to the cecum and left flexure, although in one subject it was necessary to repeat colonic administration because of unexpectedly high plasma drug levels on the first occasion. The possible reasons for this abnormal response are discussed. The mean systemic availability of oxprenolol was 82% after colonic compared with oral dosing, although marked differences were observed in individual plasma levels following drug administration by the 2 routes. The results of this study support the concept of extending the duration of oxprenolol release from a rate-controlled dosage form to permit once-daily administration with this short elimination half-life drug.