Methylphenidate is a racemic mixture comprised of the d- and l-threo enantiomers. The d-threo enantiomer is more pharmacologically active than the l-threo enantiomer.

Methylphenidate HCI is a central nervous system (CNS) stimulant.

The mode of therapeutic action in humans is not completely understood, but methylphenidate presumably activates the brain stem arousal system and cortex to produce its stimulant effect. Methylphenidate is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

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.

Pharmacokinetics

Absorption

Methylin Oral Solution (methylphenidate hcl oral solution 5 mg/5 ml and 10 mg/5 ml) is readily absorbed. Following oral administration of Methylin Oral Solution (methylphenidate hcl oral solution 5 mg/5 ml and 10 mg/5 ml) , peak plasma methylphenidate concentrations are achieved at 1 to 2 hours. Methylin Oral Solution (methylphenidate hcl oral solution 5 mg/5 ml and 10 mg/5 ml) has been shown to be bioequivalent to Ritalin® tablet. The mean Cmax following a 20 mg dose is approximately 9 ng/mL.

Food Effect

In a study in adult volunteers to investigate the effects of a high-fat meal on the bioavailability of Methylin Oral Solution (methylphenidate hcl oral solution 5 mg/5 ml and 10 mg/5 ml) at a dose of 20 mg, the presence of food delayed the peak by approximately 1 hour (1.7 hours, fasted and 2.7 hours, fed). Overall, a high-fat meal increased the Cmax of Methylin Oral Solution (methylphenidate hcl oral solution 5 mg/5 ml and 10 mg/5 ml) by about 13% and the AUC by about 25%, on average. Through a cross-study comparison, the magnitude of increase in Cmax and AUC is found to be comparable between the Methylin Oral Solution (methylphenidate hcl oral solution 5 mg/5 ml and 10 mg/5 ml) and Ritalin®, the immediate release tablet.

Metabolism and Excretion

In humans, methylphenidate is metabolized primarily via deesterification to alpha-phenylpiperidine acetic acid (PPA, ritalinic acid). The metabolite has little or no pharmacologic activity.

After oral dosing of radiolabeled methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main urinary metabolite was PPA, accounting for approximately 80% of the dose.

The pharmacokinetics of the Methylin Oral Solution (methylphenidate hcl oral solution 5 mg/5 ml and 10 mg/5 ml) have been studied in healthy adult volunteers. The mean terminal half-life (t½) of methylphenidate following administration of 20 mg Methylin (t½ = 2.7 hours) is comparable to the mean terminal t½ following administration of Ritalin® (methylphenidate hydrochloride immediate-release tablets) (t½ = 2.8h) in healthy adult volunteers.

Special Populations

Gender - The effect of gender on the pharmacokinetics of methylphenidate after Methylin Oral Solution (methylphenidate hcl oral solution 5 mg/5 ml and 10 mg/5 ml) administration has not been studied.

Race - The influence of race on the pharmacokinetics of methylphenidate after Methylin Oral Solution (methylphenidate hcl oral solution 5 mg/5 ml and 10 mg/5 ml) administration has not been studied.

Age - The pharmacokinetics of methylphenidate after Methylin Oral Solution (methylphenidate hcl oral solution 5 mg/5 ml and 10 mg/5 ml) administration have not been studied in pediatrics.

Renal Insufficiency

There is no experience with the use of Methylin Oral Solution (methylphenidate hcl oral solution 5 mg/5 ml and 10 mg/5 ml) in patients with renal insufficiency. After oral administration of radiolabeled methylphenidate in humans, methylphenidate was extensively metabolized and approximately 80% of the radioactivity was excreted in the urine in the form of ritalinic acid. Since renal clearance is not an important route of methylphenidate clearance, renal insufficiency is expected to have little effect on the pharmacokinetics of Methylin Oral Solution (methylphenidate hcl oral solution 5 mg/5 ml and 10 mg/5 ml) .

Hepatic Insufficiency

There is no experience with the use of Methylin Oral Solution (methylphenidate hcl oral solution 5 mg/5 ml and 10 mg/5 ml) in patients with hepatic insufficiency.

Last reviewed on RxList: 11/29/2010
This monograph has been modified to include the generic and brand name in many instances.