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Pharmacokinetics, pharmacodynamics, long-term efficacy and safety of oral 1-deamino-8-D-arginine vasopressin in adult patients with central diabetes insipidus.

Abstract：

:1. The pharmacokinetics and pharmacodynamics of intranasal (IN) and oral 1-deamino-8-D-arginine vasopressin (DDAVP) were compared in 10 Chinese adults with central diabetes insipidus previously controlled on IN DDAVP. This was followed by comparison of the acute pharmacodynamics of commonly used oral preparations (containing 100, 200 and 400 micrograms per tablet) and a 1 year prospective evaluation of the long-term safety and efficacy of oral DDAVP. 2. Following 20 micrograms IN and 200 micrograms orally, respective plasma DDAVP concentrations peaked after 45.6 +/- 7.3 and 93.3 +/- 3.3 (mean +/- s.e.mean) min, reaching 24.1 +/- 4.7 and 15.1 +/- 3.2 pmol 1(-1) and respective terminal half-lives were 2.2 +/- 0.1 and 2.0 +/- 0.1 h. Based on the area under the concentration-time-curve, the bioequivalent IN/oral ratio was 1:16. 3. As judged by changes in urine flow rate and osmolality after IN or oral (100, 200 or 400 micrograms) DDAVP, antidiuretic activity increased rapidly during the second hour and peaked at 4 h. The antidiuresis duration and magnitude correlated with the oral dose (P < 0.001 and < 0.05 respectively), and was least following 100 micrograms (P < 0.01 vs 200 or 400 micrograms). Increasing the dose from 200 to 400 micrograms did not increase maximal antidiuretic activity significantly, but there was a trend towards a longer duration of action (P = 0.076). 4. During the 1-year prospective study with oral DDAVP 300-600 micrograms per day in two to three doses, stable and satisfactory antidiuresis (comparable with that on previous IN therapy) was maintained; tablets were well-tolerated and no side-effect warranted drug withdrawal. 5. These findings suggest that the 100 and 200 micrograms preparations of oral DDAVP are adequate for the long-term control of central diabetes insipidus in our population, and that the 400 micrograms preparation may have a role if the frequency of administration is to be reduced.

journal_name

Br J Clin Pharmacol

journal_title

British journal of clinical pharmacology

authors

Lam KS,Wat MS,Choi KL,Ip TP,Pang RW,Kumana CR

doi

10.1046/j.1365-2125.1996.39914.x

subject

Has Abstract

pub_date

1996-09-01 00:00:00

pages

379-85

issue

eissn

0306-5251

issn

1365-2125

journal_volume

pub_type

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Pharmacokinetics, pharmacodynamics, long-term efficacy and safety of oral 1-deamino-8-D-arginine vasopressin in adult patients with central diabetes insipidus.