178 Single-Dose Pharmacokinetics of Amphetamine Extended-Release Tablet Compared with Amphetamine Extended-Release Oral Suspension

Abstract:Objectives:Evaluate comparative bioavailability of single-dose amphetamine extended-release tablet (AMPH ER TAB, Tris Pharma, Inc., Monmouth Junction, NJ) 20 mg, swallowed whole or chewed and amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; and evaluate whether a PK food effect exists on AMPH ER TAB (contains a 3.2:1 ratio of d- to l-amphetamine).METHODS:Healthy volunteers (18-55 yr) were randomized to 1 dose of AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg AMPH EROS (fasted).A crossover design was used. Samples were collected each period pre-dose and at time points to 60 h post-dose. D-and l-amphetamine were measured, and PK was calculated (90% CIs of the ratios of the geometric mean plasma levels) for Cmax, AUCt, and AUC0∞. Comparative bioavailability was determined when ratios were within 80 and 125%. Safety was also assessed.RESULTS:32 subjects completed the study. Based on the calculated bioavailability ratios, for AMPH ER TAB swallowed vs. AMPH EROS fasted: d-amphetamine total and peak exposures were found to be similar: AUC0-t: 100.68-108.08%, AUC0-∞:101.47-109.52%, Cmax: 98.10-103.17%. For l-amphetamine, the total and peak exposures were similar: AUC0-t: 100.31-108.57%, AUC0-∞:101.27-111.09%, Cmax: 98.2-103.37%.AMPH ER TAB chewed vs. AMPH EROS fasted: For d-amphetamine, the total and peak exposures were similar: AUC0-t: 99.23-106.62%, AUC0-∞: 99.58-107.59%, Cmax: 99.91-105.14%. For l-amphetamine, the total and peak exposure was similar: AUC0-t: 98.16-106.35%, AUC0-∞: 98.44-108.11%, Cmax: 99.53-104.75%.Food effect: AMPH ER TAB, chewed, fasted vs. fed: For d-amphetamine, the total and peak exposure was similar: AUC0-t: 92.57-99.49%, AUC0-∞: 91.12-98.48%, Cmax: 94.22-99.17%.For l-amphetamine, the total and peak exposure was similar: AUC0-t: 91.27-98.91%, AUC0-∞: 88.44-97.17%, Cmax: 94.52-99.50%).No serious AEs were reported during the conduct of this study, and the AE profiles were observed to be similar in frequency of events and severity to other amphetamine formulations used in ADHD.CONCLUSIONS:Bioavailability of single dose of AMPH ER TAB for both d- and l-amphetamine was comparable, swallowed whole or chewed, to an equivalent 20 mg dose of the reference product AMPH EROS, 2.5 mg/mL fasted, and showed equivalent peak and overall exposure.No food effect was observed for AMPH ER TAB administered chewed. All AEs were mild in severity and AE profiles were similar to other amphetamine formulations used for treatment of ADHD.Funding Acknowledgements:Tris Pharma, Inc.

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Comparative Bioavailability of Amphetamine Extended-Release Oral Suspension and Extended-Release Mixed Amphetamine Salts

CNS Spectrums ◽

10.1017/s109285292000262x ◽

2021 ◽

Vol 26 (2) ◽

pp. 163-163

Author(s):

Antonio Pardo ◽

Mohammed Bouhajib ◽

Eman Rafla ◽

Thomas R. King ◽

Judith C. Kando

Keyword(s):

Single Dose ◽

Safety Assessment ◽

Extended Release ◽

Healthy Adult ◽

Geometric Mean ◽

Oral Suspension ◽

Open Label ◽

Post Dose ◽

Comparative Bioavailability ◽

The Mean

AbstractPurposeThis open-label, single-dose, randomized, two-period, two-treatment, two-sequence, crossover study evaluated the comparative bioavailability between amphetamine extended-release oral suspension (treatment A: AMPH EROS, Dyanavel XR 2.5 mg/mL, 18.8 mg amphetamine base per 7.5 mL) and extended-release mixed amphetamine salts (treatment B: ER MAS, Adderall XR 30 mg capsules, equivalent to 18.8 mg amphetamine base per capsule) after a single dose in healthy adult subjects, under fasted conditions.MethodsThe crossover design allowed for intra-subject PK comparisons. Relative comparable bioavailability was determined by a statistical comparison of the AUC and Cmax parameters for both d- and l-amphetamine, where the geometric mean ratios for AUC and Cmax were within the 90% confidence limits (80.0%–125.0%) to determine comparable bioavailability between test products. Subjects in sequence 1 received treatment A followed by B; subjects in sequence 2 received treatment B followed by treatment A. PK samples were obtained at 0 (pre-dose) through 60 hours post-dose. The safety assessment was based on reported frequency and severity of adverse events.ResultsThirty (30) subjects were enrolled and 28 completed. The mean age of subjects was 35 years, with a mean BMI of 25.9 kg/m2. Most subjects were Male (63.3%) and Black (56.7%). The geometric mean ratios for Cmax and all AUC measurements were within the 80–125% bound indicating comparable bioavailability between both test products. Both test products were generally well-tolerated with no serious AEs reported.ConclusionsThe bioavailability of a single 7.5 mL dose of AMPH EROS 2.5 mg/mL was comparable to a single 30 mg capsule dose of ER MAS. AMPH EROS (both d- and l-amphetamine) showed equivalent peak and overall exposure to ER MAS under fasted conditions.FundingTris Pharma, Inc.

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2.18 Single-Dose Pharmacokinetics of Amphetamine Extended-Release Tablet Compared With Amphetamine Extended-Release Oral Suspension

Journal of the American Academy of Child & Adolescent Psychiatry ◽

10.1016/j.jaac.2018.09.106 ◽

2018 ◽

Vol 57 (10) ◽

pp. S164

Author(s):

Barry K. Herman ◽

Judith C. Kando ◽

Thomas R. King ◽

Antonio Pardo

Keyword(s):

Single Dose ◽

Extended Release ◽

Oral Suspension ◽

Extended Release Tablet ◽

Release Tablet

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Single-dose pharmacokinetics of amphetamine extended-release tablets compared with amphetamine extended-release oral suspension

CNS Spectrums ◽

10.1017/s1092852919001676 ◽

2020 ◽

Vol 25 (6) ◽

pp. 774-781

Author(s):

Antonio Pardo ◽

Judith C. Kando ◽

Thomas R. King ◽

Eman Rafla ◽

Barry K. Herman

Keyword(s):

Single Dose ◽

Adverse Events ◽

Extended Release ◽

Food Effect ◽

Relative Bioavailability ◽

Oral Suspension ◽

Plasma Samples ◽

Serious Adverse Events ◽

Time Points ◽

Extended Release Tablet

AbstractObjectiveEvaluate the relative bioavailability of single-dose amphetamine extended-release tablet (AMPH ER TAB) 20 mg, swallowed whole or chewed, and amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; evaluate food effect on AMPH ER TAB.MethodsHealthy volunteers (18–55 years) were randomized to 1 dose of AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg AMPH EROS (fasted). A crossover study design was used. Plasma samples were collected each period predose and at time points to 60 hours postdose. d- and l-amphetamine were measured and pharmacokinetic (PK) was calculated (90% confidence intervals of the ratios of the plasma levels) for AUC0-t, AUC0-∞, and Cmax. Comparative relative bioavailability between formulations was determined when ratios were within 80% and 125%. Safety was also assessed.ResultsThirty-two subjects completed the study. AMPH ER TAB swallowed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 100.68% to 108.08%, AUC0-∞: 101.47% to 109.52%, Cmax: 98.10% to 103.17%; l: AUC0-t: 100.31% to 108.57%, AUC0-∞: 101.27% to 111.09%, Cmax: 98.2% to 103.37%. For d- and l-amphetamine when the tablet is swallowed whole, Tmax was 5.00 hours (with a range of 2.00–9.00 hours). AMPH ER TAB chewed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 99.23% to 106.62%, AUC0-∞: 99.58% to 107.59%, Cmax: 99.91% to 105.14%; l: AUC0-t: 98.16% to 106.35%, AUC0-∞: 98.44% to 108.11%, Cmax: 99.53% to 104.75%. For d- and l-amphetamine when the tablet has been chewed, Tmax was 5.00 hours (with a range of 3.00-7.00 hours). PK results were similar for patients in the fasted and fed groups, indicative of no presence of food effect. No serious adverse events (AEs) were reported, overall AE profiles between the tablet and oral suspension were comparable without any unanticipated safety concerns.ConclusionsSingle doses of AMPH ER TAB for both d- and l-amphetamine demonstrated comparable bioavailability to a 20 mg dose of AMPH EROS, 2.5 mg/mL under fasted conditions when chewed and swallowed whole, and demonstrated equivalent peak and overall exposure without apparent food effect. AMPH ER TAB was well-tolerated and consistent with adverse events noted in other amphetamine formulations.

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A Single-Dose, Comparative Bioavailability Study Comparing Amphetamine Extended-Release Oral Suspension with Extended-Release Mixed Amphetamine Salts Capsules

CNS Spectrums ◽

10.1017/s1092852920002060 ◽

2020 ◽

pp. 1-22

Author(s):

Antonio Pardo ◽

Mohammed Bouhajib ◽

Thomas R. King ◽

Eman Rafla ◽

Judith C. Kando

Keyword(s):

Single Dose ◽

Extended Release ◽

Oral Suspension ◽

Bioavailability Study ◽

Comparative Bioavailability ◽

Comparative Bioavailability Study

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Comparison of Azithromycin Pharmacokinetics following Single Oral Doses of Extended-Release and Immediate-Release Formulations in Children with Acute Otitis Media

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00692-11 ◽

2011 ◽

Vol 55 (11) ◽

pp. 5022-5026 ◽

Cited By ~ 7

Author(s):

Ping Liu ◽

Annie F. Fang ◽

Robert R. LaBadie ◽

Penelope H. Crownover ◽

Adriano G. Arguedas

Keyword(s):

Single Dose ◽

Otitis Media ◽

Extended Release ◽

Geometric Mean ◽

Acute Otitis Media ◽

Lower Boundary ◽

Systemic Exposure ◽

Immediate Release ◽

Oral Suspension ◽

Tolerability Profile

ABSTRACTAn azithromycin extended-release (ER) oral suspension was developed to improve the gastrointestinal tolerability profile without substantially compromising systemic exposure. A single dose of 30 mg/kg azithromycin immediate-release (IR) oral suspension has been used in children to treat acute otitis media (AOM). This study was conducted to compare the pharmacokinetics of a 60-mg/kg azithromycin ER single dose with a 30-mg/kg azithromycin IR single dose in children with AOM aged 6 months to 6 years (n= 19 per treatment). Serum samples were collected at 1, 2, 3, 4, 8, 24, 48, and 72 h after dosing. The area under the curve from time zero to 72 h postdosing (AUC0-72) was calculated based on a noncompartmental method. One-way analysis of variance (ANOVA) was used to compare exposure parameters (e.g., AUC0-72and peak concentration) as well as concentrations at each time point. The adjusted geometric mean ratio of the ER/IR AUC0-72was 157.98% (90% confidence interval [CI], 98.87%, 252.44%), which met the predefined criterion of the lower boundary of the 90% CI of ≥80%. As expected, due to the slower-release profile of the ER formulation, the concentrations of the ER formulation during the first 3 h were lower than those of the IR formulation. After 3 h postdosing, the lower boundaries of the 90% CI for the ER/IR concentration ratios were greater than 100%. These results indicated that a 60-mg/kg single dose of ER azithromycin provides similar or greater systemic exposure in children than the 30-mg/kg single dose of IR azithromycin.

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