Antidiuretic Effect and Pharmacokinetics of Oral 1-Desamino-8-D-Arginine Vasopressin. 1. Studies in Adults and Children

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Abstract
The dose-response relationships and pharmacokinetics of orally administeredl-desamino-8-D-AVP (DDAVP) were investigated. In water-loaded normal subjects marked reductions inurine flow rate and increases in urinary osmolality occurred. The responses were maximal 2 h afteringestion of 50, 100, and 200 µg, and lasted at least 6 h. Plasma DDAVP levels increased in a dose-dependent fashion and its disappearance from the plasma followed an exponential time course, witha half-life 86 to 142 min. In water-loaded adults with central diabetes insipidus (CDI), 200 µg oral DDAVP caused marked antidiuresis and mean urinary osmolality increased from 107 mosm/kg to 554mosm/kg after 3 h. In these patients the effect also lasted at least 6 h. Children with CDI were less sensitive than normal subjects to the 50-µg dosage and required 100 µg orally to achieve a duration of action similar to that resulting from 200 µg in adults. Oral DDAVP may be useful for treating some patients with CDI.