Pharmacokinetic and Pharmacodynamic Properties of a Micro-Dose Nasal Spray Formulation of Desmopressin (AV002) in Healthy Water-Loaded Subjects

• Published in: Pharmaceutical research Vol. 36; no. 6; pp. 92 - 8
• Main Authors: Andersson, Karl-Erik, Longstreth, James, Brucker, Benjamin M., Campeau, Lysanne, Cheng, Linda, Francis, Leo, Fein, Seymour
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2019; Springer; Springer Nature B.V
• Subjects: Administration, Intranasal; Adolescent; Adult; Analysis; Antidiuretic Agents - administration & dosage; Antidiuretic Agents - adverse effects; Antidiuretic Agents - pharmacokinetics; Antidiuretic Agents - pharmacology; Antidiuretics; Bioavailability; Biochemistry; Biological Availability; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Deamino Arginine Vasopressin - administration & dosage; Deamino Arginine Vasopressin - adverse effects; Deamino Arginine Vasopressin - pharmacokinetics; Deamino Arginine Vasopressin - pharmacology; Desmopressin; Desmopressin acetate; Dosage; Healthy Volunteers; Humans; Hyponatremia; Injection; Intranasal administration; Male; Medical Law; Nasal Sprays; Nose; Pharmacodynamics; Pharmacokinetics; Pharmacology/Toxicology; Pharmacy; Research Paper; Urine; Young Adult; antidiuresis; bioavailability; urine osmolality; hyponatremia; safety
• ISSN: 0724-8741; 1573-904X; 1573-904X
• DOI: 10.1007/s11095-019-2628-1

Purpose Antidiuretic therapy with desmopressin for nocturia has been hampered by formulations with high doses, low bioavailability and variable pharmacokinetics. AV002 (SER120), a novel, emulsified, microdose desmopressin nasal spray, with a permeation enhancer (cylcopentadecanolide), was developed to have pharmacokinetic characteristics suitable for nocturia treatment. Methods Twelve healthy subjects participated in an open-label, dose-escalating study. Water-loaded subjects were sequentially dosed every 48 h with AV002 0.5, 1.0, 2.0 μg and 0.12 μg desmopressin subcutaneous (SC) bolus injection. Results AV002 intranasal administration produced a time-to-maximum concentration (T max ) between 15 and 30 min and a maximum concentration (C max ) <10 pg/mL. C max and area under the curve showed dose proportionality. Coefficient of variation for AV002 was similar to that observed for the SC dose. Bioavailability of AV002 was approximately 8% compared to SC injection. AV002 demonstrated pharmacodynamic effects within 20 min of dosing and showed increasing magnitude and duration with escalating doses. AV002 2.0 μg had maximum median urine osmolality of 629 mOsm/kg and median urine output ≤2 mL/min for 5–6 h. Conclusions AV002 demonstrated rapid absorption, high bioavailability, limited duration of action, and low coefficient of variation, suggesting it may be a suitable formulation for nocturia treatment. Trial registration not required (single-center, phase 1).