Intranasal versus Oral Administration of Lisdexamfetamine Dimesylate A Randomized, Open-Label, Two-Period, Crossover, Single-Dose, Single-Centre Pharmacokinetic Study in Healthy Adult Men James C. Ermer, 1 Kerry Dennis, 1 Mary B. Haffey, 1 Walter J. Doll, 2 Erik P. Sandefer, 2 Mary Buckwalter, 1 Richard C. Page, 2 Brian Diehl 1 and Patrick T. Martin 1 1 Shire Development Inc., Wayne, Pennsylvania, USA 2 Scintipharma Inc., Lexington, Kentucky, USA Abstract Background and Objective: Data on pharmacokinetic parameters of the pro- drug stimulant lisdexamfetamine dimesylate via alternate routes of adminis- tration are limited. The pharmacokinetics of d-amphetamine derived from lisdexamfetamine dimesylate after single oral (PO) versus intranasal (IN) administration of lisdexamfetamine dimesylate were compared. Methods: In this randomized, two-period, crossover study, healthy men without a history of substance abuse were administered single PO or IN (radiolabelled with £100 mCi 99m Tc-diethylenetriamine-pentaacetic acid and confirmed by scintigraphy) lisdexamfetamine dimesylate 50 mg ‡7 days apart. Serial blood samples were drawn to measure d-amphetamine and intact lisdexamfetamine at 0 (pre-dose), 15, 30 and 45 minutes and at 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose for PO administration and at 0 (pre-dose), 5, 10, 15, 20, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose for IN administration. Treatment-emergent adverse events (TEAEs) were assessed. Results: Eighteen subjects were enrolled and completed the study. The mean – SD maximum observed plasma concentration (C max ) and area under the plasma concentration-time curve from time zero to time of last measurable con- centration (AUC last ) of d-amphetamine following PO administration of lis- dexamfetamine dimesylate were 37.6 – 4.54 ng/mL and 719.1 – 157.05 ng Á h/mL, respectively; after IN administration, these parameters were 35.9 – 6.49 ng/mL and 690.5 – 157.05 ng Á h/mL, respectively. PO and IN administration dem- onstrated similar median time to reach C max (t max ) for d-amphetamine: 5 hours for PO administration versus 4 hours for IN administration. Mean – SD elimination half-life (t ½ ) values were also similar for PO (11.6 – 2.8 hours) and IN (11.3 – 1.8 hours) lisdexamfetamine dimesylate. TEAEs after PO and IN administration were reported by 27.8% of subjects (5/18) and 38.9% of subjects (7/18), respectively; all AEs were mild or moderate in severity, and TEAEs such as anorexia, dry mouth, headache and nausea were consistent with known amphetamine effects. ORIGINAL RESEARCH ARTICLE Clin Drug Investig 2011; 31 (6): 357-370 1173-2563/11/0006-0357/$49.95/0 ª 2011 Adis Data Information BV. All rights reserved.