Biomedical subjects

S J Hirshey Dirksen

Publications and source records attributed to S J Hirshey Dirksen.

3 recordsLinked to original sources

PubMed2004

Dose-proportional pharmacokinetics of a methylphenidate extended-release capsule.

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.

Administration, Oral↗

PubMed2002

A postmarketing clinical experience study of Metadate CD.

OBJECTIVE: The objective of the study was to investigate the effectiveness and safety of Metadate CD (methylphenidate HCl, USP) Extended Release Capsules in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), in actual clinical practice. METHOD: This was a multicenter, open-label, postmarketing study. Eligible patients were aged 6-17 with a diagnosis of ADHD and receiving either no treatment or maintenance treatment with another approved methylphenidate (MPH) product. Metadate CD was administered once daily for 3 weeks, titrated against reported and observed symptoms. Clinical Global Impression (CGI) scores at Week 3 were used for the primary efficacy evaluation. Patient treatment satisfaction was determined by questionnaire at the final evaluation visit. Safety was assessed through adverse event reporting, laboratory tests and vital sign measurements. RESULTS: Overall, of the 308 patients in the Intent-To-Treat population, the majority (65%) demonstrated a positive response to Metadate CD (defined as CGI Global Improvement rating of very much or much improved). In addition, patients previously treated with immediate-release or extended-release tablet formulations of MPH were successfully converted to Metadate CD at a comparable dose. Most patients (87%) were very satisfied or moderately satisfied with study treatment, and among previously treated patients, 71% rated Metadate CD as much better or better than their previous MPH treatment. Adverse events were consistent with current FDA-approved product labeling for Metadate CD. CONCLUSIONS: Metadate CD is effective and well-tolerated in actual clinical use for ADHD.

Adolescent↗

PubMed2002

Methylphenidate bioavailability from two extended-release formulations.

OBJECTIVE: The objective of these studies was to compare the rate and extent of absorption of d,l-threo-methylphenidate (MPH) from two extended-release products--a capsule formulation containing coated beads and an OROS tablet formulation--in healthy male and female subjects under fasted conditions. MATERIALS: Metadate CD (methylphenidate HCl, USP) Extended-Release Capsules and Concerta (methylphenidate hydrochloride) Extended-Release Tablets. METHODS: Two studies were conducted: (1) A single dose, randomized, two-way crossover study in 36 adults comparing a 20 mg capsule and an 18 mg tablet, and (2) a single dose, randomized, four-way crossover study in 24 adults comparing 2 x 20 mg capsules, one 36 mg tablet, 3 x 20 mg capsules and one 54 mg tablet. Blood samples were collected over 24 hours and MPH plasma concentrations were used to calculate pharmacokinetic parameters for each treatment. Equivalence of pharmacokinetic parameters for comparable doses of the formulations was concluded if the 90% confidence intervals (CI) for the ratio between test and reference means were within the 80-125% equivalence criterion. RESULTS: Both formulations exhibited biphasic plasma concentration-time profiles and were equivalent in terms of total exposure (AUC(0-last) and AUC(0-infinity)). However, early exposure (AUC(0-4) and AUC(0-6), the first maximum measured plasma concentration (C(max-1), and early plasma MPH concentrations (1.5, 3 and 4 hours) were greater with the capsule formulation, while later plasma MPH concentrations (8, 10 and 12 hours) were greater with the tablet formulation (the CIs were outside the 80-125% required for equivalence and p < 0.001 for all). Similar results were obtained whether or not the data were normalized for the difference in total dose. CONCLUSIONS: The two formulations are not bioequivalent. The capsule fonnulation produces greater exposure to MPH and higher MPH concentrations during the first 6 hours following dosing. MPH is frequently used in school children, and this period would correspond to a major part of the school day.

Absorption↗