Metadate (Methylphenidate Hydrochloride) - Description and Clinical Pharmacology

DESCRIPTION

METADATE ER Tablets (methylphenidate hydrochloride extended-release tablets, USP) are a mild central nervous system (CNS) stimulant. METADATE ER is available as extended-release tablets of 10 and 20 mg for oral administration.

Methylphenidate hydrochloride is methyl α-phenyl-2-piperidineacetate hydrochloride, and its structural formula is:

Methylphenidate hydrochloride is a white, odorless, fine crystalline powder. Its solutions are acid to litmus. It is freely soluble in water and in methanol, soluble in alcohol, and slightly soluble in chloroform and in acetone. Its chemical formula is C₁₄H₁₉NO₂•HCl, and its molecular weight is 269.77.

Inactive Ingredients: Cetyl alcohol, ethylcellulose, anhydrous lactose and magnesium stearate.

CLINICAL PHARMACOLOGY

METADATE ER is a mild central nervous system stimulant.

The mode of action in man is not completely understood, but methylphenidate presumably activates the brain stem arousal system and cortex to produce its stimulant effect.

There is neither specific evidence which clearly establishes the mechanism whereby methylphenidate produces its mental and behavioral effects in children, nor conclusive evidence regarding how these effects relate to the condition of the central nervous system.

METADATE ER in extended-release tablets is more slowly but as extensively absorbed as in the regular tablets. Bioavailability of METADATE 20 mg Extended-Release Tablets was compared to a sustained-release reference product and an immediate-release product. The extent of absorption for the three products was similar, and the rate of absorption of the two sustained-release products was not statistically different.

In another reported study with a brand of Methylphenidate HCl sustained-release, the time to peak rate in children was reported as 4.7 hours (1.3 - 8.2 hours) for the sustained-release tablet dosage form and 1.9 hours (0.3 - 4.4 hours) for immediate release tablets. An average of 67% of a sustained-release tablet dosage form was excreted in children compared to 86% in adults.

Based on rate of bioavailability (AUC_0→∞ T_max, and C_max), no significant statistical difference was found following single dose administration, in fasting and fed adults, of two METADATE 10 mg Extended-Release Tablets, or one methylphenidate hydrochloride, USP sustained-release 20 mg tablet. The administration of the extended-release methylphenidate HCl, USP, tablets with food, resulted in a greater C_max and AUC_0→∞ than when administered in a fasting condition.

Pharmacokinetic and statistical analyses for a multiple dose study demonstrated that 3 times daily administration of two METADATE 10 mg Extended-Release Tablets met the requirements for bioequivalence to one methylphenidate hydrochloride, USP sustained-release 20 mg tablet when administered every eight hours. Pharmacokinetic parameters (i.e., AUC_0→∞, C_max, C_min, and C_av) demonstrated achievement of steady state following 3 times daily administration of two METADATE 10 mg Extended-Release Tablets was confirmed.

In a clinical study involving adult subjects who received Extended-release (ER) tablets, plasma concentrations of methylphenidate hydrochloride’s major metabolite appeared to be greater in females than in males. No gender differences were observed for methylphenidate hydrochloride’s plasma concentration in the same subjects.