PHARMACOKINETICS, PHARMACODYNAMICS, LONG-TERM EFFICACY AND SAFETY OF ORAL 1-DEAMINO-8-D-ARGININE VASOPRESSIN IN ADULT PATIENTS WITH CENTRALDIABETES-INSIPIDUS

1 The pharmacokinetics and pharmacodynamics of intranasal (IN) and ora l 1-deamino-8-D-arginine vasopressin (DDAVP) were compared in 10 Chine se adults with central diabetes insipidus previously controlled on IN DDAVP. This was followed by comparison of the acute pharmacodynamics o f commonly used oral preparations (containing 100, 200 and 400 mu g pe r tablet) and a 1 year prospective evaluation of the long-term safety and efficacy of oral DDAVP. 2 Following 20 mu g IN and 200 mu g 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-cur ve, the bioequivalent IN/oral ratio was 1:16. 3 As judged by changes i n urine flow rate and osmolality after IN or oral (100, 200 or 400 mu g) DDAVP, antidiuretic activity increased rapidly during the second ho ur and peaked at 4 h. The antidiuresis duration and magnitude correlat ed with the oral dose (P < 0.001 and < 0.05 respectively), and was lea st following 100 mu g (P < 0.01 vs 200 or 400 mu g). Increasing the do se from 200 to 400 mu g did not increase maximal antidiuretic activity significantly, but there was a trend towards a longer duration of act ion (P = 0.076). 4 During the 1-year prospective study with oral DDAVP 300-600 mu g per day in two to three doses, stable and satisfactory a ntidiuresis (comparable with that on previous IN therapy) was maintain ed; tablets were well-tolerated and no side-effect warranted drug with drawal. 5 These findings suggest that the 100 and 200 mu g preparation s of oral DDAVP are adequate for the long-term control of central diab etes insipidus in our population, and that the 400 mu g preparation ma y have a role if the frequency of administration is to be reduced.