Prolongation of antidiuretic response to desmopressin acetate by iontophoretic transdermal delivery in rats.
An iontophoretic drug delivery system was compared with intranasal, oral and subcutaneous delivery from a standpoint of the prolongation of the antidiuretic response to desmopressin acetate (DDAVP) in diabetes insipidus rats. Iontophoretic delivery was comparable to the nasal route at a dose about five times higher than the nasal route dose, and was 2 to 3 times as effective as the oral route. Effect of dose and duration of current application on the prolongation of the response to DDAVP was also investigated in order to find the effectiveness of the iontophoresis. The antidiuretic response to DDAVP delivered by iontophoresis indicated a dose-dependent prolongation and was prolonged up to about 14 h with the increase of the duration of current application; when a pulsed direct current at 0.1 mA was passed for about 1 h, the response to DDAVP was prolonged for about 9 h. DDAVP in the anodic donor steeply decreased with the application for 1 h, and then gradually decreased. We suggest that the antidiuretic response to DDAVP can be effectively controlled by regulating the absorption of DDAVP at the short-term iontophoresis rather than prolonged treatment.
Nakakura
M
M
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Sunto-gun, Shizuoka, Japan.
Kato
Y
Y
Ito
K
K
D000279:Administration, Cutaneous; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage* / Q000494:pharmacology; D018500:Diabetes Insipidus, Nephrogenic / Q000188:drug therapy* / Q000503:physiopathology; D004231:Diuresis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007478:Iontophoresis; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012076:Renal Agents / Q000008:administration & dosage* / Q000494:pharmacology; D013997:Time Factors
D012076:Renal Agents; D003894:Deamino Arginine Vasopressin