Methylin (Methylphenidate Hydrochloride) - Description and Clinical Pharmacology

CII

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DESCRIPTION

Methylphenidate hydrochloride is a mild central nervous system (CNS) stimulant, available for oral administration as tablets of 5 mg, 10 mg, and 20 mg and as extended-release tablets of 10 mg and 20 mg. Methylphenidate hydrochloride is methyl α-phenyl-2-piperidineacetate hydrochloride, and its structural formula is

Methylphenidate Hydrochloride USP 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.

Inactive Ingredients

Methylin^® tablets: lactose monohydrate, magnesium stearate, microcrystalline cellulose, and talc.

Methylin^® ER tablets: hydroxypropyl methylcellulose 2208, magnesium stearate, microcrystalline cellulose, and talc.

CLINICAL PHARMACOLOGY

Methylin is a mild central nervous system stimulant.

The mode of action in man is not completely understood, but Methylin 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 Methylin produces its mental and behavioral effects in children, nor conclusive evidence regarding how these effects relate to the condition of the central nervous system.

Methylphenidate hydrochloride in the ER tablets is more slowly but as extensively absorbed as in the regular tablets. Bioavailability of Methylin ER 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. Relative bioavailability of the extended-release tablet compared to the immediate-release tablet, measured by the urinary excretion of methylphenidate major metabolite (α-phenyl-2-piperidine acetic acid) was 105% (49% to 168%) in children and 101% (85% to 152%) in adults. The time to peak rate in children was 4.7 hours (1.3 to 8.2 hours) for the extended-release tablets and 1.9 hours (0.3 to 4.4 hours) for the tablets. An average of 67% of extended-release tablet dose was excreted in children as 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 Methylin ER 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 Methylin ER 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→∞, T_max, C_max, C_min, and C_av) demonstrated achievement of steady state following 3 times daily administration of two Methylin ER 10 mg Extended-Release Tablets was confirmed.

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