Administration of antidiuretic peptide (DDAVP) by way of suction de-epithelialised skin

• Published in: The Lancet (British edition) Vol. 337; no. 8756; pp. 1506 - 1509
• Main Authors: Svedman, P., Svedman, Ch, Lundin, S.
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 22.06.1991; Lancet; Elsevier Limited
• Subjects: Administration, Cutaneous; Adult; Argipressin; Bioavailability; Biological and medical sciences; Deamino Arginine Vasopressin - administration & dosage; Deamino Arginine Vasopressin - analogs & derivatives; Deamino Arginine Vasopressin - blood; Deamino Arginine Vasopressin - pharmacokinetics; Deamino Arginine Vasopressin - urine; Dermis; Diabetes insipidus; Diabetes Insipidus - drug therapy; Drug delivery; Drug delivery systems; Drugs; Epidermis; Epithelium; Evaluation Studies as Topic; Female; Forearm; General pharmacology; Humans; Hyperemia; Injections, Intradermal; Intravenous administration; Intravenous infusion; Male; Medical research; Medical sciences; Microcirculation; Middle Aged; Penetration; Peptides; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Skin; Skin Absorption; Skin spot; Suction; Suction - instrumentation; Suction - methods; Transdermal medication; Vacuum; Vasopressin; Human; Delivery system; Transdermal system; Pharmaceutical technology; Excision; Peptide hormone; Epithelium; Normal; Vasopressin; Percutaneous route; Antidiuretic; Analog; Skin; Pharmacokinetics
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/0140-6736(91)93197-H

Transdermal drug delivery seems a promising way of achieving complete, predictable absorption, but the epidermis is a barrier for most drugs. A new technique for transdermal drug delivery, in which a small patch of epidermis was removed, was tested in seven healthy volunteers by means of the antidiuretic peptide 1-deamino-8-D-arginine vasopressin (DDAVP). The epithelium of a small area of forearm skin (diameter 5 mm) was removed painlessly, and in a standard way, by a simple device operating at a preset vacuum. DDAVP was given by way of improvised occlusive reservoirs. Plasma DDAVP concentration/time curves conformed closely with zero-order kinetics, which suggests that the bioavailability approached 100%, corresponding to that for direct intravenous infusion. Four volunteers were given DDAVP daily for 4 days by way of the de-epithelialised site; there were no signs that re-epithelialisation hindered permeation. All plasma DDAVP values substantially exceeded the lowest effective therapeutic concentration for patients with diabetes insipidus. The vacuum removal of the epithelium caused pronounced hyperaemia in the de-epithelialised dermis (assessed by laser doppler flow measurement); the hyperaemia persisted, unaffected by DDAVP, and may have contributed to the efficient permeation. The skin spot appeared normal at 6 weeks.