Abstract
Abstract The effects of the proteolytic enzyme inhibitors, aprotinin, soybean trypsin inhibitor and camostat mesilate, as absorption enhancers of transdermal iontophoretic delivery of vasopressin (AVP) and its analogue, 1-deamino-8- d -arginine vasopressin (1-d-8-DAVP) were examined in rats. The dermal absorption of AVP and 1-d-8-DAVP was determined to induce an antidiuretic effect. Administration of AVP (0.5 IU/rat) or 1-d-8-DAVP (0.1 μg/rat) on abdominal skin (available diffusion area 3.14 cm 2 ) produced no antidiuretic effect. This resulted in a slight antidiuretic influence with iontophoresis (drug phase, anode; reference phase, cathode; constant current of 1 mA 3.14 cm 2 ). Moreover, the antidiuretic effect was further enhanced on application of iontophoresis and camostat mesilate (1–50 mM). However, aprotinin and soybean trypsin inhibitor had no influence on the antidiuretic effect. The activities of aminopeptidase, cathepsin B and trypsin in dermal tissue were determined to be 1.7 nmol/min per mg protein, 0.5 nmol/min per mg protein and 2.4 pmol/min per mg protein, respectively. Camostat mesilate significantly inhibited the activities of aminopeptidase and trypsin, whilst aprotinin and soybean trypsin inhibitor resulted in considerable inhibition of the activity of trypsin. Aprotinin (Mol. Wt 6500) and soybean trypsin inhibitor (Mol. Wt 8000), both having a relatively high molecular weight, may not permeate into the dermal tissue. In contrast, a small degree of absorption of camostat mesilate (about 3% 2 h) with iontophoresis might inhibit the proteolytic enzyme activity in dermal tissue and hence might enhance the dermal absorption of AVP and 1-d-8-DAVP.
Published Version
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