Pharmacokinetic Characterization and Dose Selection of a Novel Sumatriptan Nasal Spray Formulation, DFN‐02. (9th June 2017)

• Record Type: Journal Article
• Authors: Pal, Arindam; Gautam, Anirudh; Munjal, Sagar
• Is Part Of: Journal of clinical pharmacology. Volume 57:Number 11(2017)
• Page Start: 1472
• Page End: 1478
• Publication Date: 2017-06-09
• Subjects: sumatriptan -- DDM -- intranasal -- pharmacokinetics -- tolerability; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.946
• Languages: English
• ISSNs: 0091-2700

Abstract

Abstract: This 3‐way, single‐dose, randomized crossover study evaluated the pharmacokinetics (PK) and dose proportionality of 5‐, 10‐, and 15‐mg doses of intranasal sumatriptan (DFN‐02) coformulated with a permeation enhancer (DDM) in 18 healthy adults. The objective was to determine which DFN‐02 dose approximates the PK of a 6‐mg dose of sumatriptan delivered via subcutaneous injection in the deltoid muscle of the arm. Sumatriptan plasma concentrations peaked with DFN‐02 between 10 and 15 minutes postdose, declining thereafter, with a t1/2 of about 2.5 hours; mean Cmax and AUC0–∞ values increased linearly across doses. After DFN‐02 doses of 5, 10, and 15 mg, mean Cmax was 40.7 ± 14.2, 71.2 ± 22.1, and 101.0 ± 49.5 ng/mL, and mean AUC0–∞ was 49.9 ± 20.6, 87.1 ± 31.2, and 120.5 ± 53.3 ng·h/mL, respectively. The increase in sumatriptan bioavailability was less than dose‐proportional among the DFN‐02 doses studied. Based on the established PK of a 6‐mg subcutaneous sumatriptan injection (mean Tmax, 12 minutes; mean Cmax, 74 ± 15 ng/mL in the deltoid area of the arm) and the peak and time to peak sumatriptan concentrations of the DFN‐02 doses tested, a 10‐mg dose of DFN‐02 was found to be the closest match. Overall, DFN‐02 was well tolerated at doses of 5 to 15 mg, and no new safety concerns were identified.