2). Maximum plasma concentrations of guanfacine were attained at a median of 6 h after administration of GXR alone or in combination with LDX. The 90 % CI of the GMR of AUC0–∞ for guanfacine following GXR administered alone and in combination

with LDX was 0.981–1.162 and met strict bioequivalence criteria requiring 90 % CIs to fall within the interval of 0.80–1.25. The 90 % CI of the GMR of C max for guanfacine following administration of GXR alone and in combination with LDX was 1.066–1.321 and did not fall within the standard bioequivalence reference interval. The upper bound of the 90 % CI of C max for guanfacine exceeded the standard range for bioequivalence by 7 % when GXR was coadministered with LDX. Fig. 2 Mean guanfacine plasma concentrations over time following administration

of guanfacine extended release (GXR) alone and in combination with lisdexamfetamine PF-573228 dimesylate (LDX). A time shift has been applied to the figure; values have been slightly staggered on the x-axis for clarity, as some values were similar between the two treatment regimens 3.2.2 Results for d-Amphetamine and Lisdexamfetamine The mean d-amphetamine plasma concentrations following administration of LDX alone were Selleckchem MK-0457 essentially identical to those following coadministration with GXR (Fig. 3a). Maximum plasma concentrations ABT 263 of d-amphetamine were attained at a median of 4 h following dosing of LDX alone or in combination with GXR. The 90 % CIs of the GMRs for C max and AUC0–∞ for d-amphetamine following administration of LDX alone

and in combination with GXR (0.967–1.019 and 0.983–1.06, respectively) met strict bioequivalence criteria requiring 90 % CIs to fall within the interval of 0.80–1.25. Fig. 3 a Mean d-amphetamine plasma concentrations and b mean lisdexamfetamine dimesylate (LDX) plasma concentrations over time following administration of LDX alone and in combination with Quisqualic acid guanfacine extended release (GXR). A time shift has been applied to the figure; values have been slightly staggered on the x-axes for clarity, as some values were similar between the two treatment regimens Similar profiles for mean plasma LDX concentrations were obtained for regimen B (LDX alone) and regimen C (LDX and GXR) (Fig. 3b). When LDX was given alone and in combination with GXR, its mean maximum concentrations were 26.14 and 27.13 ng/mL, respectively, and were obtained at 1.1 h. 3.3 Safety Results 3.3.1 Treatment-Emergent Adverse Events A total of 18 subjects (42.9 %) reported at least one TEAE. TEAEs were reported in seven subjects (17.5 %), eight subjects (19.5 %), and 10 subjects (24.4 %) while they were receiving GXR, LDX, and GXR and LDX in combination, respectively. The most commonly reported individual TEAEs (occurring in ≥5 % of subjects during any regimen) were dizziness (5.0, 7.3, and 7.3 %), postural dizziness (10.0, 2.4, and 0 %), and headache (7.5, 4.9, and 7.