Influence of Food-intake on Desmopressin Oral Tablets and MELT-formulation
Status:
Completed
Trial end date:
2010-04-01
Target enrollment:
Participant gender:
Summary
Alarm-treatment as well as Desmopressin, a synthetic analogue of human vasopressin, are
considered the only evidence-based medicine (EBM) IA treatments in monosymptomatic nocturnal
enuresis (MNE). Desmopressin exists in three different formulations for ambulant use: nasal
spray, tablet and lyophilisate (MELT) each with differences in bioavailability (spray 2%,
tablet 0.2%, MELT 0.5%). There 's insufficient evidence to confirm the actually used
bioequivalent doses ( 10µg spray = 120µg MELT= 0.2mg tablet).
Although so frequently used, very few pharmacokinetic and -dynamic data on desmopressin are
available for children.
Due to prolonged half life, associated with waterintoxication,the nasal spray has a black box
warning from the FDA and is no longer recommended . For some authors oral formulations appear
to be a safer alternative. However, based on clinical experience of less response rate with
oral formulations, lower biodisponibility is suspected. Adult research confirms low
bioavailability of tablets but also show major influences by food-intake and changes in
gastro-intestinal motility.
To achieve maximum efficacy, recommendations are to take desmopressin tablet 1 hour before
bedtime and 2 hours after meal: this is unrealistic in schoolaged children since there never
is 3 hours between evening meal and bedtime.
In 2005 a dose response study demonstrated superior pharmaco-kinetic and dynamic properties
for desmopressin Lyophilisate MELT formula.
Since these results implicate superior action of MELT, often a change to MELT is recommended
if there is a suboptimal response with tablet: sublingual absorption would eliminate the
influence of food-intake.
However, for this statement there's no evidence, since these tests were all conducted in
children in fasting condition. Only one clinical study demonstrates bioequivalence for MELT
and tablet.
Hypothesis is that desmopressin MELT formulation has a better bioavailability when
administered together with meal due to its sublingual absorption.