Pharmacokinetics and Pharmacodynamics of the Oral Disintegrating Tablet of Desmopressin in Adults with Nocturnal Polyuria: A Pilot Study.

Abstract

The higher sensitivity to desmopressin (dDAVP) found in women and older patients with nocturnal polyuria (NP) has partially been unraveled, leading to adaptation of the dosage based on gender. However, besides age and gender, other factors might play a role in differences in sensitivity and side effects. The aim of this study is to design a pharmacokinetic/pharmacodynamic (PD) assay to identify appropriate treatment for different groups of patients, primarily dependent on differences in age and gender. This interventional pilot study was carried out in Ghent University Hospital, Belgium, between 2011 and 2013. Patients with NP were subjected to a water load test (15 mL/kg), as well as an administration of 120 µg dDAVP oral disintegrating tablet (ODT) followed by blood analysis to determine plasma dDAVP levels and urine analysis for diuresis rate, osmolality, free water clearance and sodium clearance. Six female and six male patients were included (range 30-89 years old; mean age 69 years; SD 18). Three groups based on plasma dDAVP levels were found: (1) high (only women), (2) intermediate (only men) and (3) low plasma levels. For the nighttime samples (3-12 h after intake) men presented with significantly higher variation in PD response, whereas 12-15 h after dDAVP ODT intake women presented with a less predictable outcome, although all patients but one (female) have a prolonged PD effect. This study suggests the need for individualized dose titration rather than fixed dose regimens in NP patients with bothersome symptoms. Gender, body weight and results of nocturnal free water and sodium clearance need to be taken into account for more accurate individualized treatment to result in high response rates and low side effects.