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
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
- Novartis Pharmaceuticals Corporation. Ritalin Summary of Product Characteristics. Last updated April 2018.
- Flynn Pharma Ltd. Medikinet Summary of Product Characteristics. Last updated January 2017.
- Novartis Pharmaceuticals Corporation. Ritalin LA Summary of Product Characteristics. Last updated April 2018.
- Flynn Pharma Ltd. Amfexa Summary of Product Characteristics. Last updated July 2016.
- Auden Mckenzie (Pharma Division) Ltd. Dexamfetamine Sulphate Summary of Product Characteristics. Last updated April 2018.
- Paladin Labs Inc. Dexedrine Product Monograph. Last updated March 2016.
- 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.
- Purdue Pharma. Biphentin Product Monograph. Last updated April 2017.
- 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.
- Janssen Inc. Concerta XL Summary of Product Characteristics. Last updated July 2018.
- 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.
- Gonzalez MA, Pentikis HS, Anderl N, et al. Methylphenidate bioavailability from two extended-release formulations. Int J Clin Pharmacol Ther 2002; 40: 175-184.
- Shire Pharmaceuticals Ltd. Equasym XL Summary of Product Characteristics. Last updated June 2018.
- Flynn Pharma Ltd. Medikinet XL Summary of Product Characteristics. Last updated March 2017.
- 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.
- Novartis Pharmaceuticals Corporation. Focalin XR US Prescribing Information. Last updated January 2017.
- 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.
- Shire Pharmaceuticals Ltd. Elvanse Summary of Product Characteristics. Last updated April 2018.
- Shire Pharmaceuticals Ltd. Elvanse Adult Summary of Product Characteristics. Last updated November 2017.
- 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.
- Adderall XR Canadian Product Monograph. Last updated June 2017.
- 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.
- Eli Lilly and Company Ltd. Strattera Summary of Product Characteristics. Last updated May 2015.
- 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.
- Shire Pharmaceuticals Ltd. Intuniv Summary of Product Characteristics. Last updated February 2018.
- 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.