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Pharmacokinetic Characterization and Dose Selection of a Novel Sumatriptan Nasal Spray Formulation, DFN-02.

Authors
  • Pal, Arindam1
  • Gautam, Anirudh2
  • Munjal, Sagar3
  • 1 Proprietary Products, Dr. Reddy's Laboratories, Ltd., Telangana, India. , (India)
  • 2 Proprietary Products, Dr. Reddy's Laboratories, SA., Basel, Switzerland. , (Switzerland)
  • 3 Dr. Reddy's Laboratories, Inc., Princeton, NJ, USA.
Type
Published Article
Journal
Journal of clinical pharmacology
Publication Date
Nov 01, 2017
Volume
57
Issue
11
Pages
1472–1478
Identifiers
DOI: 10.1002/jcph.946
PMID: 28597922
Source
Medline
Keywords
License
Unknown

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.

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