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Pharmacokinetic Characterization and Dose Selection of a Novel Sumatriptan Nasal Spray Formulation, DFN‐02
Author(s) -
Pal Arindam,
Gautam Anirudh,
Munjal Sagar
Publication year - 2017
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.946
Subject(s) - sumatriptan , pharmacokinetics , medicine , bioequivalence , anesthesia , nasal spray , bioavailability , crossover study , nasal administration , pharmacology , agonist , placebo , receptor , alternative medicine , pathology
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 t 1/2 of about 2.5 hours; mean C max and AUC 0–∞ values increased linearly across doses. After DFN‐02 doses of 5, 10, and 15 mg, mean C max was 40.7 ± 14.2, 71.2 ± 22.1, and 101.0 ± 49.5 ng/mL, and mean AUC 0–∞ 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 T max , 12 minutes; mean C max , 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.