ESPN 51th Annual Meeting

ESPN 2018


 
DOES ONE SIZE OF DESMOPRESSIN ORAL LYOPHILISATE FORMULATION REALLY FITS THEM ALL? EXPLORING THE NEED TO PERFORM PHARMACOKINETIC- AND PHARMACODYNAMICS TRIALS IN CHILDREN.
Dossche Lien 2 Michelet Robin 1 Raes Ann 2 De Bruyne Pauline 2 Vande Walle Johan 2

1- LABORATORY OF MEDICAL BIOCHEMISTRY AND CLINICAL ANALYSIS, DEPARTMENT OF BIOANALYSIS, FACULTY OF PHARMACEUTICAL SCIENCES, GHENT UNIVERSITY, GHENT, BELGIUM
2- DEPARTMENT OF PEDIATRIC NEPHROLOGY, GHENT UNIVERSITY HOSPITAL, GHENT, BELGIUM
 
Introduction:

Desmopressin (dDAVP) is indicated for central diabetes insipidus and primary enuresis. Patients suffering from nocturnal polyuria, all start with a dose of 120 micrograms. This lack size dependent labelling remains to be elucidated. It might be attributed to insufficient pediatric pharmacokinetics/dynamics (PK/PD) data in the whole group. 

Material and methods:

An open label, non-randomized, PK/PD study. 22 children were recruited (age 6 months – 8 years, mean age 4.8 years). All needed a urinary concentration test or had nocturnal polyuria with treatment failure on tablet. Maximal diluting capacity (urinary osmolality < 200 mosm/l) was achieved after a 15 ml/kg water load. dDAVP was provided sublingual as one-time age-adapted dose (60 (6 months - 2 years), 120 (2- 4 years), or 240 micrograms (4- 8 years)). Subsequently, all urinary voids were compensated. Plasma and urinary concentration of dDAVP were measured every 15 minutes during the first hour, and at 1h, 2h, 3h, 5h, 6h and 7h post-dosing. Non-compartmental analysis was performed, with assessment of covariates (age, sex, body weight) on PK and PD model parameters. 

Results:

PK-parameters in this younger age-group were comparable with those reported. No significant correlation (Spearman’s rank correlation coefficient) was shown between plasma concentrations of dDAVP and dose corrected by age, sex and body weight. When dose was corrected by distribution volume, a significant correlation (p < 0,01) for weight, length and age was found, not for body-mass index. It suggests that distribution volume is lower or bioavailability is higher. On PD-level, a prolonged duration (> 7h) of antidiuretic effect was found.

Conclusions:

To prescribe safely dDAVP in young children, performing studies to correlate the PK-parameters with the effect on the PD-level are essential. A longer duration of antidiuretic effect is clinically important, since ability to regain diluting capacity the next morning might be lost, increasing the risk of hyponatremia.