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Home | Disease management » Pharmacological therapy » Pharmacokinetics

This section summarises key pharmacokinetic data for the following ADHD pharmacological treatments:

  • Immediate-release methylphenidate preparations (Ritalin®, Medikinet®)
  • Immediate-release dexamfetamine preparations (Amfexa®, Dexedrine®)
  • Extended-release methylphenidate preparations (Biphentin®, Concerta XL®, Equasym XL®, Medikinet XL®, Ritalin LA®)
  • Dexmethylphenidate (Focalin XR®)
  • Lisdexamfetamine sulphate (prodrug) (Elvanse®/Elvanse Adult®)
  • Extended-release mixed amfetamine salts (Adderall XR®)
  • Atomoxetine (Strattera®)
  • Prolonged-release guanfacine (Intuniv®).

Information on peak plasma concentrations and elimination half-lives has been sourced from product documentation and published data.

  • The majority of published literature reports pharmacokinetic data in healthy adult subjects – for consistency, this section focuses on data from healthy adult subjects, where available, although this is not necessarily the population for which treatment is indicated.
  • Again, for consistency, this section focuses on data from fasted subjects, where plasma concentrations were monitored over a minimum of 24 hours following the administration of a single dose of treatment.
  • Where more than one published study was identified, the one with the largest sample size is presented.

Not all treatments are licensed for use in all countries: please refer to local prescribing information.

Immediate-release methylphenidate preparations (e.g. Ritalin®, Medikinet®)

Immediate-release methylphenidate preparations include Ritalin®, Medikinet® and potentially other marketed products.1,2 Methylphenidate is rapidly absorbed following oral administration, with peak plasma concentrations achieved in an average of 1–2 hours.1,2

  • The mean elimination half-life of methylphenidate is 2 hours.1,2
  • The pharmacokinetics of methylphenidate are similar in children and adults.1,2

Immediate-release dexamfetamine preparations (e.g. Amfexa®, Dexedrine®)

Dexamfetamine preparations include Amfexa®, Dexedrine® and potentially other marketed products.4-6

Following oral administration of Amfexa®:4

  • On average, the peak plasma concentration of dexamfetamine is achieved in 1.5 hours.
  • The average elimination half-life of dexamfetamine is 10.2 hours.
  • Note: literature searches did not identify pharmacokinetic studies of Dexedrine Spansules6 (a sustained-release formulation of dexamfetamine).

Extended-release methylphenidate preparations: Biphentin®

Following oral administration of Biphentin® in fasted adults, peak plasma concentrations of methylphenidate are achieved in 1.7 hours.8

A study of Biphentin® 80 mg in healthy, fasted adults (n=26) has reported a time to peak plasma concentration of 2.0 hours and a mean elimination half-life of 5.1 hours.9

Note: 80 mg/day is the maximum dose indicated in adults with ADHD in Canada. A maximum dose of 60 mg/day is generally indicated in children/adolescents with ADHD.

Extended-release methylphenidate preparations: Concerta XL®

Following oral administration of Concerta XL® in adults, there are two phases of methylphenidate release.10

  • An initial maximum plasma concentration is reached in ~1–2 hours.
  • The peak plasma concentration is achieved in ~6–8 hours.

The elimination half-life of methylphenidate is approximately 3.5 hours after administration of Concerta XL®.10

NOTE: Matoride XL® is bioequivalent to Concerta XL®,11 and so can be considered to have a similar pharmacokinetic profile.

Extended-release methylphenidate preparations: Equasym XL®

Following oral administration of Equasym XL®, there are two phases of methylphenidate release:13

  • On average, an initial maximum plasma concentration is reached in 1–2 hours.13
  • The peak plasma concentration is achieved in 4.5 hours in most subjects.13

The mean elimination half-life of methylphenidate is 2 hours.13

Extended-release methylphenidate preparations: Medikinet XL®

Medikinet XL® should be administered with food to prolong its action and avoid plasma peaks;14 therefore, data are presented here for fed subjects.

Following oral administration of Medikinet XL® in adults, there are two phases of methylphenidate release: a sharp initial increase in plasma concentrations, and a second rising portion approximately 3 hours later.14

The average elimination half-life of methylphenidate is approximately 3.2 hours.14

Extended-release methylphenidate preparations: Ritalin LA®

Following oral administration of Ritalin LA®, there are two peaks in plasma methylphenidate concentrations, approximately 4 hours apart. In studies with Ritalin LA® and Ritalin® tablets in adults, methylphenidate from Ritalin® tablets is eliminated from the plasma with an average half-life of about 3 hours (range 1.3 to 7.7 hours). In children, the average half-life is about 2.5 hours, with a range of about 1.5 to 5.0 hours.3

  • The elimination half-life of methylphenidate is 2.5–3.5 hours.3
  • The pharmacokinetics of methylphenidate are similar in children and adults.3

Dexmethylphenidate: Focalin XR®

Following oral administration of Focalin XR® in adults, there are two phases of dexmethylphenidate release:16

  • The first peak plasma concentration is achieved in 1.5 hours (range: 1–4 hours).16
  • The second peak plasma concentration is achieved in 6.5 hours (range: 4.5–7 hours).16

The mean elimination half-life of dexmethylphenidate is just over 3 hours (2–3 hours in children).16

Lisdexamfetamine sulphate: Elvanse®/Elvanse Adult®

Following oral administration of Elvanse®/Elvanse Adult®:18,19

  • The peak plasma concentration of d-amfetamine is achieved in 3.8 hours.18,19,*
  • The elimination half-life is <1 hour for lisdexamfetamine and 11 hours for d-amfetamine.18,19

The pharmacokinetics of d-amfetamine are similar in children and adolescent patients (Elvanse®) and healthy adult volunteers (Elvanse Adult®).18,19

Extended-release mixed amfetamine salts: Adderall XR®

Following oral administration of Adderall XR® in adults:21

  • Peak plasma concentration is achieved in 7 hours for d-amfetamine and 8 hours for l-amfetamine (both 7 hours in children aged 6–12 years with ADHD).21
  • The elimination half-life is 10 hours for d-amfetamine and 13 hours for l-amfetamine (9 and 11 hours, respectively, in children aged 6–12 years with ADHD).21

Atomoxetine: Strattera®

Following oral administration of Strattera®:24

  • The peak plasma concentration of atomoxetine is achieved in approximately 1–2 hours.23
  • The mean elimination half-life of atomoxetine is 3.6 hours in extensive metabolisers and 21 hours in poor metabolisers.23

The pharmacokinetics of atomoxetine in children and adolescents are similar to those in adults.23

Prolonged-release guanfacine: Intuniv®

Following oral administration of Intuniv® in children and adolescents (aged 6–17 years):25

  • The peak plasma concentration of guanfacine is achieved in approximately 5 hours.25
  • The mean elimination half-life of guanfacine is approximately 18 hours.25
  1. Novartis Pharmaceuticals Corporation. Ritalin Summary of Product Characteristics. Last updated April 2018.
  2. Flynn Pharma Ltd. Medikinet Summary of Product Characteristics. Last updated January 2017.
  3. Novartis Pharmaceuticals Corporation. Ritalin LA Summary of Product Characteristics. Last updated April 2018.
  4. Flynn Pharma Ltd. Amfexa Summary of Product Characteristics. Last updated July 2016.
  5. Auden Mckenzie (Pharma Division) Ltd. Dexamfetamine Sulphate Summary of Product Characteristics. Last updated April 2018.
  6. Paladin Labs Inc. Dexedrine Product Monograph. Last updated March 2016.
  7. Wong YN, Wang L, Hartman L, et al. Comparison of the single-dose pharmacokinetics and tolerability of modafinil and dextroamphetamine administered alone or in combination in healthy male volunteers. J Clin Pharmacol 1998; 38: 971-978.
  8. Purdue Pharma. Biphentin Product Monograph. Last updated April 2017.
  9. Adjei A, Teuscher NS, Kupper RJ, et al. Single-dose pharmacokinetics of methylphenidate extended-release multiple layer beads administered as intact capsule or sprinkles versus methylphenidate immediate-release tablets (Ritalin((R))) in healthy adult volunteers. J Child Adolesc Psychopharmacol 2014; 24: 570-578.
  10. Janssen Inc. Concerta XL Summary of Product Characteristics. Last updated July 2018.
  11. Schapperer E, Daumann H, Lamouche S, et al. Bioequivalence of Sandoz methylphenidate osmotic-controlled release tablet with Concerta® (Janssen-Cilag). Pharmacol Res Perspect 2015; 31: e00072.
  12. Gonzalez MA, Pentikis HS, Anderl N, et al. Methylphenidate bioavailability from two extended-release formulations. Int J Clin Pharmacol Ther 2002; 40: 175-184.
  13. Shire Pharmaceuticals Ltd. Equasym XL Summary of Product Characteristics. Last updated June 2018.
  14. Flynn Pharma Ltd. Medikinet XL Summary of Product Characteristics. Last updated March 2017.
  15. Haessler F, Tracik F, Dietrich H, et al. A pharmacokinetic study of two modified-release methylphenidate formulations under different food conditions in healthy volunteers. Int J Clin Pharmacol Ther 2008; 46: 466-476.
  16. Novartis Pharmaceuticals Corporation. Focalin XR US Prescribing Information. Last updated January 2017.
  17. Tuerck D, Wang Y, Maboudian M, et al. Similar bioavailability of dexmethylphenidate extended (bimodal) release, dexmethyl-phenidate immediate release and racemic methylphenidate extended (bimodal) release formulations in man. Int J Clin Pharmacol Ther 2007; 45: 662-668.
  18. Shire Pharmaceuticals Ltd. Elvanse Summary of Product Characteristics. Last updated April 2018.
  19. Shire Pharmaceuticals Ltd. Elvanse Adult Summary of Product Characteristics. Last updated November 2017.
  20. Krishnan S, Zhang Y. Relative bioavailability of lisdexamfetamine 70-mg capsules in fasted and fed healthy adult volunteers and in solution: a single-dose, crossover pharmacokinetic study. J Clin Pharmacol 2008; 48: 293-302.
  21. Adderall XR Canadian Product Monograph. Last updated June 2017.
  22. Haffey MB, Buckwalter M, Zhang P, et al. Effects of omeprazole on the pharmacokinetic profiles of lisdexamfetamine dimesylate and extended-release mixed amphetamine salts in adults. Postgrad Med 2009; 121: 11-19.
  23. Eli Lilly and Company Ltd. Strattera Summary of Product Characteristics. Last updated May 2015.
  24. Witcher JW, Long A, Smith B, et al. Atomoxetine pharmacokinetics in children and adolescents with attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 2003; 13: 53-63.
  25. Shire Pharmaceuticals Ltd. Intuniv Summary of Product Characteristics. Last updated February 2018.
  26. Swearingen D, Pennick M, Shojaei A, et al. A phase I, randomized, open-label, crossover study of the single-dose pharmacokinetic properties of guanfacine extended-release 1-, 2-, and 4-mg tablets in healthy adults. Clin Ther 2007; 29: 617-625.

Date of preparation: March 2019; Job code: INTSP/C-ANPROM/NBU/16/0049c

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