Comparative Pharmacodynamics and Plasma Concentrations of d-threo-Methylphenidate Hydrochloride After Single Doses of d-threo-Methylphenidate Hydrochloride and d,l-threo-Methylphenidate Hydrochloride in a Double-Blind, Placebo-Controlled, Crossover Laboratory School Study in Children With Attention-Deficit/Hyperactivity Disorder

Quinn, Declan; Wigal, Sharon B.; Swanson, James M.; Hirsch, Sharon; Ottolini, Yvonne; Dariani, Maghsoud; Roffman, Mark; Zeldis, Jerome B.; Cooper, Thomas B.

doi:10.1097/01.chi.0000140455.96946.2b

Cited by 73 publications

(47 citation statements)

References 13 publications

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“…Unlike our findings, an earlier study of dl-MPH versus d-MPH PK reported comparable plasma d-MPH concentrations (Quinn et al, 2004). A range of experimental design differences between the 2004 study and our 2013 study limit direct comparisons.…”

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confidence: 56%

“…Food has been reported to delay the d-MPH time to maximum plasma concentration and may increase total MPH exposure (Midha et al, 2001;Teo et al, 2004). Third, the earlier study by Quinn et al (2004) used children with ADHD (n = 32). Exposure to d-MPH has been reported to be "somewhat lower" in children than in adults (Focalin, 2015).…”

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confidence: 99%

“…Significant PK sex dimorphisms have been reported for a range of MPH formulations (Markowitz et al, 2003;Patrick et al, 2007). Fifth, the study by Quinn et al (2004) used relatively few plasma sampling times during the period of high drug exposure: 0.5, 1, 1.5, 2, and 4 hours (and 8 and 10 hours). The study by Patrick et al (2013) included these sampling times in addition to 2.5, 3, 5, and 6 hours (and 8, 10, and 12 hours).…”

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confidence: 99%

“…Such differences include the following. First, Quinn et al (2004) administered d-MPH or dl-MPH in extemporaneously compounded capsules. The mean time to maximum plasma concentration for d-MPH from capsules has been reported to be 1.8 hours (n = 30), compared with 1.1 hours (n = 9) for tablets (http://www.accessdata.fda.…”

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confidence: 99%

“…gov/drugsatfda_docs/nda/2001/21-278_Focalin.cfm). Second, the study by Quinn et al (2004) dosed the subjects with breakfast; the study by Patrick et al (2013) provided a light breakfast 1 hour before dosing. Food has been reported to delay the d-MPH time to maximum plasma concentration and may increase total MPH exposure (Midha et al, 2001;Teo et al, 2004).…”

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confidence: 99%

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Absorption Differences between Immediate-Release Dexmethylphenidate and dl-Methylphenidate

Patrick

Straughn

2016

Drug Metabolism and Disposition

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The postulate that twice the milligram/kilogram dose of dlmethylphenidate (dl-MPH) would result in equal exposure to d-MPH compared with half that milligram/kilogram dose of the chiral switch product dexmethylphenidate (d-MPH) was tested. Using a randomized, crossover study design, 12 men and 12 women received either immediate-release (IR) dl-MPH (0.3 mg/kg) or IR d-MPH (0.15 mg/kg). Relative bioavailability comparisons included partial area under the plasma concentration-time curves (pAUC 0-3 h ) for d-MPH. The pAUC 0-3 h is a new regulatory metric presently only required for bioequivalence testing of a specific dl-MPH modified-release product. The geometric mean ratios for both the C max and area under the plasma concentration-time curve (AUC 0-' ) were within the 90% confidence interval (CI) regulatory range of 0.8-1.25, indicating that these two drugs were bioequivalent in terms of d-MPH. However, the pAUC 0-3 h geometric mean ratio for d-MPH after IR dl-MPH versus IR d-MPH was 0.76 (P < 0.001; 90% CI, 0.67-0.87), showing significantly less early exposure to the d-isomer than IR d-MPH. The 1-hour d-MPH concentration after dl-MPH was 56% of that after the enantiopure drug. The maximum d-MPH plasma concentration (C max ) for dl-MPH was also significantly lower for dl-MPH (P < 0.05; CI, 1.02-1.19), whereas the AUC 0-' ratio of 0.89 was not significantly different (P = 0.21; CI, 0.98-1.13). The AUC 0-3 h difference reported here points to the potential limitations of using bioequivalence for sound predictions of dose-response relationships. Knowledge of the greater early exposure to d-MPH after the pure d-isomer drug compared with the racemate may contribute to drug individualization/optimization in the treatment of attention deficit hyperactivity disorder.

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confidence: 56%

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confidence: 99%

Section: Downloaded Frommentioning

confidence: 99%

Section: Downloaded Frommentioning

confidence: 99%

Section: Downloaded Frommentioning

confidence: 99%

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Absorption Differences between Immediate-Release Dexmethylphenidate and dl-Methylphenidate

Patrick

Straughn

2016

Drug Metabolism and Disposition

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Effects of Methylphenidate on Response to Oral Levodopa

Nutt¹,

Carter²,

Carlson³

2007

Arch Neurol

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To determine if repeated dosing with methylphenidate hydrochloride (MPD) (Ritalin; Novartis Pharmaceuticals, East Hanover, NJ), an inhibitor of the dopamine transporter, would augment the effects of oral levodopa in patients with Parkinson disease. Design: The study was a double-blind, randomized, placebo-controlled crossover trial. Setting: The trial was conducted at the General Clinical Research Center (GCRC) as an inpatient study. Subjects: Thirteen people with idiopathic Parkinson disease and a fluctuating motor response to levodopa were recruited from movement disorder clinics as a convenience sample. One subject was excluded because he did not have a 10% increase in tapping speed in response to levodopa. The remaining 12 subjects completed the protocol.

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