Comparison of incidence of hyponatremia between intranasal and oral desmopressin in patients with central diabetes insipidus

Abstract

ARGININE VASOPRESSIN (AVP) is the antidiuretic hormone which is synthesized in the magnocellular neurons in the supraoptic and paraventricular nuclei [1,2]. AVP is axonally transported to the posterior pituitary, released into the systemic circulation, and acts through V2 receptor in the kidney in order to promote reabsorption of free water [1,2]. The osmoregulation of AVP release is so precise that increases in plasma osmolality of only 1-2% lead to increases in plasma AVP [1,3,4]. As a result, plasma osmolality in most cases is controlled at levels of around 280 mOsm/kg, which is the threshold of AVP release [1,3,4].The deficiency of AVP causes a disorder called cen- Abstract. Central diabetes insipidus (CDI), which is characterized by polyuria and polydipsia, is caused by a deficiency of the antidiuretic hormone arginine vasopressin (AVP). While CDI is treated with desmopressin, an analogue of AVP, the intranasal formulation is inconvenient and CDI patients reportedly prefer the oral formulation to the intranasal one. In Japan, intranasal desmopressin had been the only formulation for the treatment of CDI until 2012, when the desmopressin orally disintegrating tablet (ODT) was approved for treatment. In this study we analyzed 26 patients with CDI in whom intranasal desmopressin was switched to desmopressin ODT. The mean daily dose of intranasal desmopressin was 10 ± 8 μg/day, and that of desmopressin ODT was 142 ± 59 μg/day. The mean serum sodium levels were 140 ± 5 mmol/L and 140 ± 3 mmol/L with intranasal desmopressin and desmopressin ODT, respectively, and there were no significant differences between these values. The frequency of hyponatremia (<135 mmol/L) with intranasal desmopressin was 11.7% and that with desmopressin ODT was 7.6%, while the frequency of hyponatremia (<130 mmol/L) with intranasal desmopressin was 4.2% and that with desmopressin ODT was 1.3%. Statistical analyses revealed that incidence of hyponatremia was significantly decreased after the switch to desmopressin ODT. Thus, it is suggested that water balance is better controlled with desmopressin ODT than with intranasal desmopressin in patients with CDI.Key words: Desmopressin, Central diabetes insipidus, Hyponatremia, Vasopressin tral diabetes insipidus (CDI), which is characterized by polyuria accompanied by thirst and polydipsia [5,6]. Patients with CDI are treated with desmopressin, an analogue of AVP, which is usually given twice or three times per day [7]. The concentration of desmopressin in blood reaches a peak soon after administration, and the antidiuretic action remains maximal for several hours [8][9][10][11]. Due to the pharmacokinetics/pharmacodynamics of desmopressin, its most frequent side effect in the treatment of CDI is hyponatremia [12,13].In Japan, intranasal desmopressin had been the only formulation for the treatment of CDI until 2012, when desmopressin orally disintegrating tablet (ODT) was approved for treatment. Because the efficiency and safety of desmopressin ODT have been demonstrated [13,14], and oral form...

Evolving pituitary hormone deficits in primarily isolated GHD: a review and experts’ consensus

“…If ADH deficiency cannot be compensated by moderately increased fluid intake or causes severe sleep disturbance, the synthetic ADH analog desmopressin is the treatment of choice. Administration routes are multiple; the preferred one is orally, as water intoxication and hyponatremia occur less likely than after intranasal administration [ 65 , 66 ]. The bioavailability of the intranasal desmopressin administration is ten times less than the intravenous administration, and ten times more than the oral administration.…”

Vasopressin-secreting neurons derived from human embryonic stem cells through specific induction of dorsal hypothalamic progenitors

“…CDI patients are treated with desmopressin, an analogue of vasopressin. However, the frequency of hyponatremia with desmopressin is not uncommon 4 . Furthermore, if CDI is accompanied by dysfunction of osmoreceptors, patients can become adipsic and show life-threatening dehydration 3 .…”

Drugs for the treatment of central diabetes insipidus: historical background and modern opportunities

“…Наиболее опасным нежелательным эффектом при применении является задержка жидкости и гипонатриемия, при этом сле-дует пропустить прием десмопрессина и дождаться выделения светлой мочи, а также умеренного ощу-щения жажды [50,60,64]. По данным исследований, О б з о р ы л и т е р а т у р ы применение интраназального спрея может более часто провоцировать развитие гипонатриемии у пациентов по сравнению с сублингвальной формой, что, однако, может также быть связано с неоднородностью исследо-ванных групп пациентов по возрасту [59].…”