OBJECTIVE: To assess the dose-proportionality of the 10 mg, 20 mg and 30 mg methylphenidate extended-release (MPH ER) capsule formulations in healthy adults. MATERIALS: Metadate CD (methylphenidate HCl, USP) extended-release capsules (10, 20 and 30 mg) were obtained from Celltech Manufacturing Inc. (Rochester, NY, USA). METHODS: This was a single-center, single-dose, fasted, randomized, open-label, 3-way crossover study with a 1-week washout period between doses, in 24 healthy male and female subjects, aged 21-40 years. MPH plasma concentration-time data were used to calculate the pharmacokinetic parameters for each treatment. The 20 mg capsule, the first FDA-approved dosage strength, was used as reference treatment. RESULTS:Twenty-three subjects completed all 3 study periods. Regardless of the dose, MPH ER capsules exhibited similar PK profiles as evidenced by a biphasic absorption profile, consisting of a sharp initial increase followed by a second increase in MPH plasma levels, all occurring at the same times. All 90% confidence intervals for the 10:20 mg and 30:20 mg dose-normalized geometric mean ratios were within the 80-125% FDA limits for bioequivalence. This was true for Cmax (maximum observed concentration), AUC(0-last) (area under the plasma concentration curve from time 0 to the last measurable time point) and AUC(0-inf) (area under the plasma concentration curve from time 0 to infinity). Adverse events were mild and the number and types of adverse events experienced by subjects did not differ among the 3 dosages. CONCLUSION: Data collected from this study demonstrate the dose proportionality of the new 10 mg and 30 mg dosage strengths of MPH ER capsules with the 20 mg capsule. The availability and predictability of these dosage strengths should facilitate dose titration of ADHD patients.
RCT Entities:
OBJECTIVE: To assess the dose-proportionality of the 10 mg, 20 mg and 30 mg methylphenidate extended-release (MPH ER) capsule formulations in healthy adults. MATERIALS: MetadateCD (methylphenidate HCl, USP) extended-release capsules (10, 20 and 30 mg) were obtained from Celltech Manufacturing Inc. (Rochester, NY, USA). METHODS: This was a single-center, single-dose, fasted, randomized, open-label, 3-way crossover study with a 1-week washout period between doses, in 24 healthy male and female subjects, aged 21-40 years. MPH plasma concentration-time data were used to calculate the pharmacokinetic parameters for each treatment. The 20 mg capsule, the first FDA-approved dosage strength, was used as reference treatment. RESULTS: Twenty-three subjects completed all 3 study periods. Regardless of the dose, MPH ER capsules exhibited similar PK profiles as evidenced by a biphasic absorption profile, consisting of a sharp initial increase followed by a second increase in MPH plasma levels, all occurring at the same times. All 90% confidence intervals for the 10:20 mg and 30:20 mg dose-normalized geometric mean ratios were within the 80-125% FDA limits for bioequivalence. This was true for Cmax (maximum observed concentration), AUC(0-last) (area under the plasma concentration curve from time 0 to the last measurable time point) and AUC(0-inf) (area under the plasma concentration curve from time 0 to infinity). Adverse events were mild and the number and types of adverse events experienced by subjects did not differ among the 3 dosages. CONCLUSION: Data collected from this study demonstrate the dose proportionality of the new 10 mg and 30 mg dosage strengths of MPH ER capsules with the 20 mg capsule. The availability and predictability of these dosage strengths should facilitate dose titration of ADHDpatients.
Authors: Sang Heon Lee; Wan Seok Seo; Hyung Mo Sung; Tae Young Choi; So Yeun Kim; So-Jeong Choi; Bon Hoon Koo; Jong Hun Lee Journal: Psychiatry Investig Date: 2012-11-12 Impact factor: 2.505