Development and evaluation of a composite dosage form containing desmopressin acetate for buccal administration

Kottke, D; Burckhardt, Bjoern B.; Knaab, Tanja C.; Breitkreutz, Jörg; Fischer, Björn

doi:10.1016/j.ijpx.2021.100082

Cited by 6 publications

(5 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the presence of polyposis and more severe disease can interfere with the local absorption of the drug. It should be noted that the bioavailability of desmopressin delivered intranasally is 5%–10% 21 . Therefore, it seems appropriate that the analyses have been adjusted for these confounders in our study.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of desmopressin on bleeding during endoscopic sinus surgery: A randomized clinical trial

Akbarpour

Jalali

Akbari

et al. 2022

Laryngoscope Investig Oto

View full text Add to dashboard Cite

Background This study aimed to evaluate the effect of local nasal desmopressin premedication on blood loss and the quality of surgical field in Functional Endoscopic Sinus Surgery (FESS). Material and methods In a randomized clinical trial, patients referred for FESS to treat their bilateral chronic rhinosinusitis were recruited. The participants were adults (≥18 years). They were randomly assigned (1:1:1) to receive low‐dose (20 μg) or high‐dose (40 μg) intranasal desmopressin (DDAVP) or placebo 60 min before the induction of general anesthesia. Standard FESS was performed by the same surgeon. The primary outcomes were volume of intraoperative bleeding and the quality of surgical field. Clean surgical field was defined as a score ≤2 on the Boezaart grading system. Results A total of 120 patients were included on an intention‐to‐treat basis (mean age: 41.0 years; 40 women, 80 men). There were no significant differences in primary outcomes between low‐dose DDAVP and placebo. As for the volume of blood loss, however, there was a significant difference between high‐dose DDAVP and placebo (mean difference: 29.6 ml; adjusted Cohen's d: −1.02; p < .001). Also, in the high‐dose DDAVP, the probability of having a good surgical field over time was about two times higher than in the placebo group (RRs for first and second surgical sides: 1.89 and 2.18). The number needed to treat for the two time points was 1.6 and 1.3, respectively. Conclusion The present study showed that the use of desmopressin at a dose of 40 μg 1 h before surgery can reduce bleeding and improve the quality of the surgical field. Further studies are recommended to be able to generalize these findings to other ENT surgeries. Level of evidence 1b.

show abstract

Section: Discussionmentioning

confidence: 99%

“…It should be noted that the bioavailability of desmopressin delivered intranasally is 5%–10%. 21 Therefore, it seems appropriate that the analyses have been adjusted for these confounders in our study. Furthermore, HD‐DDAVP caused significantly better outcomes compared to the placebo.…”

Section: Discussionmentioning

confidence: 99%

Effect of desmopressin on bleeding during endoscopic sinus surgery: A randomized clinical trial

Akbarpour

Jalali

Akbari

et al. 2022

Laryngoscope Investig Oto

View full text Add to dashboard Cite

show abstract

“…Desmopressin’s effects on life-threatening hyponatremia are particularly associated with intranasal administration, which has led to the initial approval for its use intranasally being withdrawn by the FDA [ 30 ]. Therefore, desmopressin containing minitablets with a mucoadhesive film have been developed for buccal delivery which do not require swallowing, can improve compliance [ 31 ], and have a very low incidence of hyponatremia [ 28 ]. More recently, orodispersible films and gels have been developed which, when placed on the tongue or cheek, dissolve rapidly to release drugs into the oral cavity [ 23 , 32 ].…”

Section: Oromucosal Administration Of Peptidesmentioning

confidence: 99%

Oromucosal Administration of Oxytocin: The Development of ‘Oxipops’

Xu,

Lan,

Kou

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

The role of the hypothalamic neuropeptide oxytocin in influencing the brain and behavior has been the subject of widespread research over the last few decades due, most notably, to its reported involvement in promoting social cognition and motivation, reducing anxiety, and relieving pain. It is also increasingly being considered as an important therapeutic intervention in a variety of disorders with social dysfunction as a symptom. While, in recent years, studies in humans have administered oxytocin primarily via an intranasal route, since it may partly enter the brain directly this way via the olfactory and trigeminal nerves, there is increasing evidence that many of its functional effects can be peripherally mediated via increasing its concentration in the blood. This has opened up an oromucosal administration route as an alternative, which is beneficial since the oral consumption of peptides is problematic due to their rapid breakdown in the acidic environment of the gastrointestinal system. In this review we will discuss both the methodologies we have developed for administering oxytocin via lingual application and medicated lollipops, ‘oxipops’, in terms of increasing blood concentrations and the bioavailability of the peptide, and also their validation in terms of functional effects on the brain and behavior. While areas under the curve are significantly greater in terms of plasma oxytocin concentrations following intranasally relative to oromucosally administered oxytocin, with the estimated absolute bioavailability of the latter being around 4.4% compared with 11.1% for intranasal administration, the time to peak concentrations (around 30 min) and functional effects on the brain and behavior are broadly similar. We will also discuss potential therapeutic advantages of the oromucosal administration of oxytocin in different clinical contexts and its wider application for other peptides which are increasingly being developed for therapeutic use.

show abstract

“…For calculation of the daily dose requirements, we converted the nasal and sublingual doses to the equivalent oral doses. Previous studies have found a bioavailability of 10-20 times higher with the nasal administration than with the oral form [5,9,[14][15][16]. Based on previous practice, we decided to multiply the dose with 20 when converting nasal dose to oral dose, and multiply with 1.67 when converting sublingual dose to oral dose [3,7].…”

Section: Primary Outcomementioning

confidence: 99%

Desmopressin Dose Requirements in Adults with Congenital and Acquired Central Diabetes Insipidus

Pedersen,

Andreassen,

Rasmussen

et al. 2023

Horm Metab Res

View full text Add to dashboard Cite

Central diabetes insipidus is a rare disorder characterized by a deficiency of vasopressin. The first line drug to treat this disorder is a synthetic analog of vasopressin, desmopressin.The primary aim of this retrospective register study was to compare desmopressin dose requirements in patients with acquired and congenital DI, and secondly to assess the influence of BMI on dose requirement and risk of hyponatremia with different drug administrations. We included all patients with suspected DI attending the endocrine department at Rigshospitalet, Copenhagen, Denmark in 2022. We identified 222 patients who were included whereof 130/222 (58.6 %) were female and median age was 53 years (IQR 35 to 63). The etiology included 7/222 (3.2 %) congenital and 215/222 (96.8 %) acquired. After converting nasal and sublingual doses to equivalent oral doses, the median daily dose requirement was 600 µg in patients with congenital etiology compared to 200 µg in patients with acquired etiology (p = 0.005). We found no association between BMI and desmopressin dose requirements (P=0.6). During the past 12 months, 66/215 (30.7%) had sodium levels < 136 mmol/L including 20/215 (9.3%) with sodium levels < 131 mmol/L. No increased risk of hyponatremia was found, when nasal and oral were compared (P=0.9). Daily desmopressin dose requirements were higher in patients with congenital DI compared to patients with acquired DI. However, this result was associated with uncertainty due to the small congenital group. BMI did not influence daily dose requirements and nor did type of administration influence the risk of hyponatremia.

show abstract

Development and evaluation of a composite dosage form containing desmopressin acetate for buccal administration

Cited by 6 publications

References 18 publications

Effect of desmopressin on bleeding during endoscopic sinus surgery: A randomized clinical trial

Effect of desmopressin on bleeding during endoscopic sinus surgery: A randomized clinical trial

Oromucosal Administration of Oxytocin: The Development of ‘Oxipops’

Desmopressin Dose Requirements in Adults with Congenital and Acquired Central Diabetes Insipidus

Contact Info

Product

Resources

About