Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-22T08:50:37.288Z Has data issue: false hasContentIssue false
  • English
  • Français

Single- and Multiple-Dose Pharmacokinetics of an Oral Mixed Amphetamine Salts Extended-Release Formulation in Adults

Published online by Cambridge University Press:  07 November 2014

Susan B. Clausen ,
Stephanie C. Read  and
Simon J. Tulloch
Get access Rights & Permissions [Opens in a new window]

Abstract

Objectives: Assess the bioavailability of mixed amphetamine salts extended-release (MAS XR) 30-mg capsules and the dose proportionality of pharmacokinetic measures for MAS XR 20,40, and 60 mg.

Methods: Study A, an open-label single-period study, and Study B, a randomized, open-label, three threeway crossover study, were conducted in healthy adults in a clinical research unit. In Study A, 20 subjects received a single MAS XR 30-mg capsule by mouth daily for 7 days. In Study B, 12 subjects received single oral doses of MAS XR 20,40, and 60 mg separated by 7-14-day washout periods.

Findings: Plasma dextroamphetamine (D-amphetamine) and levoamphetamine (L-amphetamine) concentrations were measured using a validated LC-MS/MS method. In Study A, a 3:1 ratio of D-amphetamine to L-amphetamine was observed for AUC0-∞ and Cmax. Tmax was 4.2 and 4.3 hours for D-amphetamine to Lamphetamine, respectively. In Study B, for D- and Lamphetamine, statistically significant differences were observed for AUC0-t, AVC0-∞, and Cmax between all doses; there was a linear relationship between pharmacokinetic variables and dose and Tmax was similar for each isomer (range: 4.5–5.3 hours) with all given MAS XR doses.

Conclusion: The extent of exposure as assessed by mean AUC0-24 and Cmax reflected the 3:1 ratio of D-amphetamine to L-amphetamine in MAS XR 30-mg capsules. The pharmacokinetic profiles of MAS XR 20, 40, and 60 mg are dose proportional for the isomers.

Type
Academic Supplement
Information
CNS Spectrums , Volume 10 , Issue S20: Mixed Amphetamine Salts Extended Release for the Treatment of ADHD in Adults: Current Evidence , December 2005 , pp. 6 - 15
Copyright
Copyright © Cambridge University Press 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. Rowland, AS, Lesesne, CA, Abramowitz, AJ. The epidemiology of attention-deficit/hyperactivity disorder (ADHD): a public health view. Ment Retard Dev Disabil Res Rev. 2002;8(3):162–170.CrossRefGoogle ScholarPubMed
2. Dulcan, M. Practice parameters for the assessment and treatment of children, adolescents, and adults with attention-deficit/hyperactivity disorder. American Academy of Child and Adolescent Psychiatry, J Am Acad Child Adolesc Psychiatry. 1997;36(suppl 10):85S–121S.CrossRefGoogle ScholarPubMed
3. Murphy, K, Barkley, R. Prevalence of, DSM-IV symptoms of, ADHD in adult licensed drivers: implications for clinical diagnosis. J Atten Disord. 1996;1:147–161.CrossRefGoogle Scholar
4. Hciligenstein, E, Conyers, LM, Berns, AR, Miller, MA, Smith, MA. Preliminary normative data on, DSM-IV attention deficit hyperactivity disorder in college students, J Am Coll Health, 1998;46(4):185–188.CrossRefGoogle Scholar
5. United States Census Bureau. Census 2000, Summary File 4. Availahle at: http://factfinder.census.gov. Accessed October 2005.Google Scholar
6. Biederman, J, Mick, E, Faraone, SV. Age dependent decline of attention deficit hyperactivity disorder: impact of remission definition and symptom subtype. Am J Psychiatry. 2000;157(5):816–818.CrossRefGoogle Scholar
7. Swanson, JM, McBurnett, K, Wigal, T, et al. Effect of stimulant medication on children with attention deficit disorder: a “review of reviews.” Exceptional Children. 1993;60:154–162.CrossRefGoogle Scholar
8. Spencer, T, Biederman, J, Wilcns, T, Harding, M, O'Donnell, D, Griffin, S. Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle. J Am Acad Child Adolesc Psychiatry. 1996;35(4):409–432.CrossRefGoogle ScholarPubMed
9. Greenhill, LL, Halperin, JM, Abikoff, H. Stimulant medications. J Am Acad Child Adolesc Psychiatry. 1999;38(5):503–512.CrossRefGoogle ScholarPubMed
10. Solanto, MV. Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav Brain Res. 1998;94(1):127–152.CrossRefGoogle ScholarPubMed
11. Kupietz, SS, Bartlik, B, Angrist, B, Winsberg, BG. Psychostimulant plasma concentration and learning performance. J Ciin Psychopharmacol. 1985;5(5):293–295.CrossRefGoogle ScholarPubMed
12. Angrist, B, Corwin, J, Bartlik, B, Cooper, T. Early pharmacokinetics and clinical effects of oral D-amphetamine in normal subjects. Biol Psychiatry. 1987;22(11): 1357–1368.CrossRefGoogle ScholarPubMed
13. Brown, GL, Hunt, RD, Ebert, MH, Bunney, WE Jr, Kopin, IJ. Plasma levels of D-amphetamine in hyperactive children. Serial behavior and motor responses. Psychopharmaeology. 1979;62(2):133–140.Google ScholarPubMed
14. Brown, GL, Ebert, MH, Mikkelsen, EJ, Hunt, RD., Behavior and motor activity response in hyperactive children and plasma amphetamine levels following a sustained release preparation. J Am Acad Child Psychiatry. 1980;19(2):225–239.CrossRefGoogle ScholarPubMed
15. Swanson, JM, Wigal, S, Greenhill, LL, et al. Analog classroom assessment of Adderall in children with, ADHD. J Am Acad Child Adolesc Psychiatry. 1998;37(5):519–526.CrossRefGoogle ScholarPubMed
16. Pelham, WE, Aronoff, HR, Midlam, JK, et al. A comparison of Ritalin and Adderall: efficacy and time-course in children with attention-deficit/hyperactivity disorder. Pediatrics. 1999;103(4):e43.CrossRefGoogle ScholarPubMed
17. Pelham, WE, Gnagy, EM, Chronis, AM, et al. A comparison of morning-only and morning/late afternoon Adderall to morning-only, twice-daily, and three timesdaily methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics. 1999;104(6):1300–1311.CrossRefGoogle ScholarPubMed
18. Manos, MJ, Short, EJ, Findling, RL. Differential effectiveness of methylphenidate and Adderall in school-age youths with attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1999;38(7):813–819.CrossRefGoogle ScholarPubMed
19. Pliszka, SR, Browne, RG, Olvera, RL, Wynne, SK. A double-blind, placebo-controlled study of Adderall and methylphenidate in the treatment of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2000;39(5):619–626.CrossRefGoogle ScholarPubMed
20. Ahmann, PA, Theye, FW, Berg, R, Linquist, AJ, Van Erem, AJ, Campbell, LR. Placebo-controlled evaluation of amphetamine mixture–dextroamphetamine salts and amphetamine salts (Adderall): efficacy rate and side effects. Pediatrics. 2001;107(1):e10.CrossRefGoogle ScholarPubMed
21. Spencer, T, Biederman, J, Wilens, T, et al. Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2001;58(8):775–782.CrossRefGoogle ScholarPubMed
22. Arnold, LE, Huestis, RD, Smeltzer, MA, Scherib, J, Wemmer, D, Coiner, Gl. Levoamphetamine vs dextroamphetamine in minimal brain dysfunction. Replication, time response, and differential effect by diagnostic group and family rating. Arch Gen Psychiatry. 1976;33(3):292–301.CrossRefGoogle ScholarPubMed
23. Arnold, LE, Kirilcuk, V, Corson, SA, Corson, EO. Levoamphetamine and dextroamphetamine: differential effect on aggression and hyperkinesis in children and dogs. Am J Psychiatry. 1973; 130(2):165–170.CrossRefGoogle ScholarPubMed
24. Arnold, LE, Wender, PH, McCloskey, K, Snyder, SH. Levoamphetamine and dextroamphetamine: comparative efficacy in the hyperkinetic syndrome. Assessment by target symptoms. Arch Gen Psychiatry. 1972;27(6):816–822.CrossRefGoogle ScholarPubMed
25. Pelham, WE Jr, Sturges, J, Hoza, J, et al. Sustained release and standard methyiphenidate effects on cognitive and social behavior in children with attention deficit disorder. Pediatrics. 1987;80(4):491–501.CrossRefGoogle ScholarPubMed
26. Swanson, JM, Kinsbourne, M, Roberts, W, Zucker, K. Time-response analysis of the effect of stimulant medication on the learning ability of children referred for hyperactivity. Pediatrics. 1978;61(1):21–29.CrossRefGoogle ScholarPubMed
27. Claxton, AJ, Cramer, J, Pierce, C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296–1310.CrossRefGoogle ScholarPubMed
28. Hack, S, Chow, B. Pediatric psychotropic medication compliance: a literature review and research-based suggestions for improving treatment compliance. J Child Adolesc Psychopharmacol 2001;11(1):59–67.CrossRefGoogle ScholarPubMed
29. Swanson, J. Compliance with stimulants for attention-deficit/hyperactivity disorder: issues and approaches for improvement. CNS Drugs. 2003;17(2):117–131.CrossRefGoogle ScholarPubMed
30. Tulloch, SJ, Zhang, Y, McLean, A, Wolf, KN. SLI381 (Adderall, XR), a two-component, extended-release formulation of mixed amphetamine salts: bioavailability of three test formulations and comparison of fasted, fed, and sprinkled administration. Pharmacotherapy. 2002;22(11):1405–1415.CrossRefGoogle ScholarPubMed
31. McCracken, JT, Biederman, J, Greenhill, LL, et al. Analog classroom assessment of a once-daily mixed amphetamine formulation, SL1381 {Adderall, XR), in children with, ADHD. J Am Acad Child Adolesc Psychiatry. 2003;42(6):673–683.CrossRefGoogle ScholarPubMed
32. Biederman, J, Lopez, FA, Boellner, SW, Chandler, MC. A randomized, double-blind, placebo-controlled, parallel-group study of, SL1381 (Adderall, XR) in children with attention-deficit/hyperactivity disorder. Pediatrics. 2002;110(2 Pt 1):258–266.CrossRefGoogle ScholarPubMed
33. McGough, JJ, Biederman, J, Greenhill, LL, et al. Pharmacokinetics of, SLI381 (Adderall, XR) an extended-release formulation of Adderall. J Am Acad Child Adolesc Psychiatry. 2003;42(6):684–691.CrossRefGoogle ScholarPubMed
34. Weisler, RH, Chrisman, AK, Wilens, TE. Adderall, XR dosed once-daily in adult patients with, ADHD. Presentation at: the 156th Annual Meeting of the American Psychiatric Association; May 20, 2003; San Francisco, CA.Google Scholar
35. Weisler, RH, Biederman, J, Chrisman, AK, et al. Long-term safety and efficacy of once-daily Adderall, XR in adults with, ADHD, Poster presented at: the 156th Annual Meeting of the American Psychiatric Association; May 17–22, 2003; San Francisco, CA. Poster NR 647.Google Scholar
36. Gough, K, Hutchison, M, Keene, O, et al. Assessment of dose proportionality: report from the statisticians in the pharmaceutical industry/pharmacokinetics, UK joint working party. Drug Inf J. 1995;29:1039–1048.CrossRefGoogle Scholar
37. Dzerk, AM, Lin, PP, Lee, JW, et al. A stereoselective, LC/MS/MS method for the quantitation of R/S amphetamine in human, EDTA plasma [abstract]. Pharm Res. 1997;14:S685.Google Scholar
38. Liang, HR, Foltz, RL, Meng, M, Bennett, P. Method development and validation for quantitative determination of methadone enantiomers in human plasma by liquid chromatography/tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;806(2):191–198.CrossRefGoogle ScholarPubMed
39. Edholm, LE, Lindberg, C, Paulson, J, Walhagen, A. Determination of drug enantiomers in biological samples by coupled column liquid chromatography and liquid chromatography-mass spectrometry. J Chromatogr. 1988;424(1):61–72.CrossRefGoogle ScholarPubMed