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 (Elvanse®/Elvanse Adult®)
- Mixed amfetamine salts (Adderall XR®)
- Atomoxetine (Strattera®)
- 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
- 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 hours1,2
- The pharmacokinetics of methylphenidate are similar in children and adults.1,2
Methylphenidate plasma concentration-time profile following two doses of Ritalin® 20 mg, administered 4 hours apart (n=16). Reproduced with kind permission.3*†
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).
Dexamfetamine plasma concentration-time profile following single doses of dexamfetamine 10 mg in healthy, fasted adults (n=24). Reproduced with kind permission.7
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 (Figure).9
Methylphenidate plasma concentration-time profile following single doses of Biphentin® 80 mg in healthy, fasted adults (n=26)9
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.
Methylphenidate plasma concentration-time profile following single doses of Concerta XL® 18–54 mg in healthy, fasted adults. Reproduced with kind permission.12
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 hours13
- 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
Methylphenidate plasma concentration-time profile following 1x, 2x or 3x Equasym XL® 20 mg in healthy, fasted adults. Reproduced with kind permission.12
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 2 hours.14
Methylphenidate plasma concentration-time profile following 2x Medikinet XL® 20 mg in healthy, fed male adults (n=26). Reproduced with kind permission.15
Extended-release methylphenidate preparations: Ritalin LA®
Following oral administration of Ritalin LA®, there are two peaks in plasma methylphenidate concentrations, approximately 4 hours apart.16
- The elimination half-life of methylphenidate is 2 hours16
- The pharmacokinetics of methylphenidate are similar in children and adults.16
Methylphenidate plasma concentration-time profile following 2x Ritalin LA® 20 mg in healthy, fasted male adults (n=27). Reproduced with kind permission.15
Dexmethylphenidate: Focalin XR®
Following oral administration of Focalin XR® in adults, there are two phases of dexmethylphenidate release:17
- The first peak plasma concentration is achieved in 1.5 hours (range: 1–4 hours)17
- The second peak plasma concentration is achieved in 6.5 hours (range: 4.5–7 hours).17
The mean elimination half-life of dexmethylphenidate is just over 3 hours (2–3 hours in children).17
Dexmethylphenidate plasma concentration-time profile following Focalin XR® 20 mg in healthy, fasted adults (n=24). Reproduced with kind permission.18
Lisdexamfetamine sulphate: Elvanse®/Elvanse Adult®
Following oral administration of Elvanse®/Elvanse Adult®:19,20
- The peak plasma concentration of d-amfetamine is achieved in 3.8 hours19,20,*
- The elimination half-life is <1 hour for lisdexamfetamine and 11 hours for d-amfetamine.19,20
The pharmacokinetics of d-amfetamine are similar in children and adolescent patients (Elvanse®) and healthy adult volunteers (Elvanse Adult®).19,20
LDX and d-amfetamine plasma concentration-time profiles following single doses of Elvanse Adult® 70 mg in healthy, fasted adults (n=18). Reproduced with kind permission.21
Mixed amfetamine salts: Adderall XR®
Following oral administration of Adderall XR® in adults:22
- 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)22
- 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).22
Amfetamine plasma concentration-time profile following single doses of Adderall XR® 20 mg in healthy, fasted adults (n=21). Reproduced with kind permission.23
Atomoxetine: Strattera®
Following oral administration of Strattera®:24
- The peak plasma concentration of atomoxetine is achieved in approximately 1–2 hours24
- The mean elimination half-life of atomoxetine is 3.6 hours in extensive metabolisers and 21 hours in poor metabolisers.24
The pharmacokinetics of atomoxetine in children and adolescents are similar to those in adults.24
Atomoxetine plasma concentration-time profile following single doses of Strattera® in adults with ADHD (n=223; extensive metabolisers; data normalised to a 1 mg/kg dose). Reproduced with kind permission.25*
Guanfacine: Intuniv®
Following oral administration of Intuniv® in children and adolescents (aged 6–17 years):26
- The peak plasma concentration of guanfacine is achieved in approximately 5 hours26
- The mean elimination half-life of guanfacine is approximately 18 hours.26
Guanfacine plasma concentration-time profile following single doses of Intuniv® 1–4 mg in healthy, fasted adults (n=49). Reproduced with kind permission.27
- Ritalin Summary of Product Characteristics. Novartis Pharmaceuticals UK Ltd. Last updated 05 May 2015.
- Medikinet Summary of Product Characteristics. Flynn Pharma Ltd. Last updated 10 September 2015.
- Wang Y, Lee L, Somma R, et al. In vitro dissolution and in vivo oral absorption of methylphenidate from a bimodal release formulation in healthy volunteers. Biopharm Drug Dispos 2004; 25: 91-98.
- Amfexa Summary of Product Characteristics. Flynn Pharma Ltd. Last updated 06 June 2016.
- Dexamfetamine Sulphate Summary of Product Characteristics. Auden Mckenzie (Pharma Division) Ltd. Last updated 01 August 2016.
- Dexedrine Product Monograph. Paladin Labs Inc. Last updated 21 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.
- Biphentin Product Monograph. Purdue Pharma. Last updated 10 June 2016.
- 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(®)) in healthy adult volunteers. J Child Adolesc Psychopharmacol 2014; 24: 570-578.
- Concerta Product Monograph. Janssen Inc. Last updated 26 February 2015.
- Matoride XL Summary of Product Characteristics. Sandoz Ltd. Last updated 02 December 2015.
- Gonzalez MA, Pentikis HS, Anderl N, et al. Methylphenidate bioavailability from two extended-release formulations. Int J Clin Pharmacol Ther 2002; 40: 175-184.
- Equasym XL Summary of Product Characteristics. Shire Pharmaceuticals Ltd. Last updated 10 March 2014.
- Medikinet XL Summary of Product Characteristics. Flynn Pharma Ltd. Last updated 17 June 2014.
- 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.
- Ritalin LA Summary of Product Characteristics. Novartis Pharmaceuticals Corporation. Last updated 29 June 2015.
- Focalin XR US Prescribing Information. Novartis Pharmaceuticals Corporation. Last updated June 2015.
- 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.
- Elvanse Summary of Product Characteristics. Shire Pharmaceuticals Ltd. Last updated 13 September 2016.
- Elvanse Adult Summary of Product Characteristics. Shire Pharmaceuticals Ltd. Last updated 13 June 2016.
- 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 23 September 2015.
- 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.
- Strattera Summary of Product Characteristics. Eli Lilly and Company Ltd. Last updated 08 June 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.
- Intuniv Summary of Product Characteristics. Last updated 10 December 2015.
- 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.
