Current Investigational Drugs for the Treatment of Attention-Deficit/Hyperactivity Disorder

Childress, Ann; Tran, Chau

doi:10.1517/13543784.2016.1147558

Cited by 24 publications

(30 citation statements)

References 54 publications

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“…The halflife was extended by more than an hour in CTx-1301 (4.5 and 4.3 hours) versus d-MPH-ER (3.0 hours) [107]. Additionally, between 8 and 24 hours post-dose, CTx-1301 maintained d-MPH levels of greater than 2 ng/mL longer than d-MPH-ER, and thereby exposure was significantly higher versus d-MPH-ER (AUC 8 DR/ER-AMP is the first evening-dosed, once-daily ER AMP formulation developed using the same DELEXIS® drug delivery platform as DR/ER-MPH [108]. The single-dose pharmacokinetics of DR/ER-AMP were evaluated over a 48hour period in adolescents and children diagnosed with ADHD and previously treated with AMP [109].…”

Section: Ctx-1301: Triple-release Multicore Formulation Of D-mphmentioning

confidence: 99%

“…d-ATS is the first transdermal patch containing d-AMP. It was found to be effective in a phase II, randomized, double-blind, placebo-controlled, crossover laboratory classroom study of youth with ADHD aged 6 to 17 years [108]. However, the pharmacokinetic properties of d-ATS are unknown, and to the best of our knowledge, no other studies have been published or presented at conferences.…”

Section: D-ats: D-amp Transdermal Patchmentioning

confidence: 99%

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An update on the pharmacokinetic considerations in the treatment of ADHD with long-acting methylphenidate and amphetamine formulations

Childress

Komolova²,

Sallee³

2019

Expert Opinion on Drug Metabolism & Toxicology

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Introduction: Long-acting stimulant formulations are recommended as first-line pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD). Over the past 20 years, extended-release (ER) methylphenidate (MPH) and amphetamine (AMP) formulations have evolved to include varying drug delivery technologies, enantiomers/salts, and dosage forms. All formulations are characterized by a unique pharmacokinetic profile that is closely mirrored by pharmacodynamic response allowing clinicians to individualize therapy based on their patient's clinical needs and dosing preferences. Areas covered: This review provides an update on the pharmacokinetic properties of approved and investigational ER MPH and AMP formulations and highlights pharmacokinetic features that clinicians should consider when selecting a long-acting stimulant. Expert opinion: Since there are no reliable biomarkers that can predict individualized response to longacting stimulants, clinicians need to consider their distinctive pharmacokinetic properties, including the pharmacokinetic profile, rate and extent of absorption, variability, dose proportionality, bioequivalence, and potential for accumulation. Clinicians also need to understand that certain factors can contribute to increased variability in pharmacokinetics and potentially affect outcomes. Less invasive, highthroughput techniques and novel time-based scales are being developed to advance research on the pharmacokinetic-pharmacodynamic relationships of stimulants. Model-based pharmacokineticpharmacodynamic approaches can be applied to aid the development of novel formulations and individualize therapy with existing drugs. ARTICLE HISTORYfor the treatment of ADHD. However, given their rapid absorption and metabolism, the therapeutic effects of IR stimulants typically wear off within a few hours, requiring twice-or thrice-daily dosing to achieve symptom control [19,20]. This presents a number of significant challenges for patients, including fluctuating peak and trough plasma concentrations that may increase the risk of adverse events or reduce efficacy; the inconvenience of multiple daily dosing, which may result in embarrassment, stigma, and lack of privacy, especially when administrating therapy during a school or work day; reduced treatment compliance; and the potential for diversion of these Schedule II drugs [17,[19][20][21][22][23][24]. Sustained-release (SR) formulations of MPH were initially developed to address these challenges. Unfortunately, they were not as effective as IR formulations and the reduced efficacy was attributed to acute tolerance due to a lack of a steep absorption phase and a flat (i.e. zero-order) drug delivery profile following peak levels [19,21,22]. Subsequently, an ascending (e.g. first-order) drug delivery profile was proposed to overcome or minimize this tachyphylaxis [21,22]. Based on this observation, several extended-release (ER) formulations of both MPH and AMP have since been developed with ascending plasma concentrations that mimic twice-or thrice-daily ad...

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Section: Ctx-1301: Triple-release Multicore Formulation Of D-mphmentioning

confidence: 99%

Section: D-ats: D-amp Transdermal Patchmentioning

confidence: 99%

An update on the pharmacokinetic considerations in the treatment of ADHD with long-acting methylphenidate and amphetamine formulations

Childress

Komolova²,

Sallee³

2019

Expert Opinion on Drug Metabolism & Toxicology

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“…Stimulants are now considered the first line pharmacologic treatment option for individuals with ADHD. 43,44 ADHD treatment has progressed from what was initially a decision between short-acting methylphenidate versus short-acting amphetamine, each of which required dosing several times per day in order to maintain therapeutic efficacy. Various strategies have been developed by pharmaceutical manufacturers to avoid the mid-day and intraday dosing.…”

Section: Prioritization For Treatment Among Comorbid Conditionsmentioning

confidence: 99%

Optimizing outcomes in ADHD treatment: from clinical targets to novel delivery systems

Mattingly

Anderson

2016

CNS Spectr.

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Our knowledge and understanding of the underlying neurobiology and symptomatic expression of ADHD has advanced dramatically over the past decade. Associated with these advances has been a similar explosion of new treatment options to individualize treatment for our patients. This article will: ∙ review strategies to measure ADHD symptoms and functional difficulties while seeking to achieve full symptomatic remission throughout the day ∙ summarize recent findings regarding the management and prioritization of ADHD and comorbid conditions and ∙ discuss the various pharmacologic treatment options with a focus on recently developed molecules and novel delivery systems.

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“…Although the prescribing information for Metadate CD allows patients to open the capsule and sprinkle the contents on applesauce, the entire contents of the capsule need to be ingested without being chewed to ensure effectiveness. 13,20 Another new methylphenidate formulation, Aptensio XR, is a oncedaily formulation that provides onset approximately 1 hour after dosing, followed by treatment coverage for up to 12 hours. To ease medication administration, alternative extended-release methylphenidate formulations have been created, including a transdermal patch, Daytrana (Noven, Miami, Florida), an oral suspension, Quillivant XR (Pfizer, New York, New York), and a chewable tablet, QuilliChew ER (Pfizer, New York, New York).…”

mentioning

confidence: 99%

“…This formulation continuously releases the active drug for over 24 hours starting approximately 8 hours after administration, a feature designed to allow patients to take the medication at bedtime and have the onset of effect the next morning. 13,20 Another new methylphenidate formulation, Aptensio XR, is a oncedaily formulation that provides onset approximately 1 hour after dosing, followed by treatment coverage for up to 12 hours. This formulation is designed for patients who require ADHD symptom control in the morning, throughout the day, and into the evening.…”

mentioning

confidence: 99%

A Comparison of the Pharmacokinetics of Methylphenidate Extended‐Release Orally Disintegrating Tablets With a Reference Extended‐Release Formulation of Methylphenidate in Healthy Adults

Childress

Stark

McMahen

et al. 2017

Clinical Pharm in Drug Dev

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Extended-release (ER) methylphenidate (MPH) is a first-line treatment for attention-deficit/hyperactivity disorder. A methylphenidate extended-release orally disintegrating tablet (MPH XR-ODT) has recently been developed. This was a randomized, open-label, 3-period, 3-treatment study comparing the bioavailability and absorption of 2 MPH XR-ODT formulations with an MPH ER reference medication. Here we report the 2 treatments comparing the commercial MPH XR-ODT formulation and reference medication. Following a ≥10-hour fast, 42 healthy adults received 60 mg of reference medication or MPH XR-ODT (2 × 30 mg). The following pharmacokinetic (PK) parameters were calculated for total methylphenidate (d + l): maximum plasma concentration (C ), time to maximum plasma concentration (T ), terminal half-life (T ), and areas under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC ), and from time zero extrapolated to infinity (AUC ). Secondary PK end points included partial AUCs. Safety was also assessed. Overall systemic exposure to methylphenidate after MPH XR-ODT administration was similar to that of the reference product, and the concentration-time profiles for MPH XR-ODT and the reference drug were similar, although the C was 25% higher for MPH XR-ODT. The most common treatment-emergent adverse events were nausea (6) and anxiety (4), which were similar across treatments.

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Current Investigational Drugs for the Treatment of Attention-Deficit/Hyperactivity Disorder

Cited by 24 publications

References 54 publications

An update on the pharmacokinetic considerations in the treatment of ADHD with long-acting methylphenidate and amphetamine formulations

An update on the pharmacokinetic considerations in the treatment of ADHD with long-acting methylphenidate and amphetamine formulations

Optimizing outcomes in ADHD treatment: from clinical targets to novel delivery systems

A Comparison of the Pharmacokinetics of Methylphenidate Extended‐Release Orally Disintegrating Tablets With a Reference Extended‐Release Formulation of Methylphenidate in Healthy Adults

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