Enantioselective aspects of the disposition of dl-threo-methylphenidate after the administration of a sustained-release formulation to children with attention deficit-hyperactivity disorder.

It has been shown previously that immediate-release dl-threo-methylphenidate (Ritalin) undergoes stereoselective disposition in human adults as well as in children with attention deficit-hyperactivity disorder. Although the sustained-release formulation of dl-threo-methylphenidate (Ritalin-SR) has been demonstrated to be effective in sustaining the attention of the children with attention deficit-hyperactivity disorder, there are no data on plasma levels of methylphenidate after administration of the sustained-release formulation. The purpose of this present investigation was twofold: (1) to determine whether the levels of methylphenidate were sustained for over a time period of 8 h, and (2) to examine enantioselective aspects of the pharmacokinetics following the ingestion of the sustained-release formulation. Six children with attention deficit-hyperactivity disorder were given 20 mg of sustained-release dl-threo methylphenidate. Plasma samples were harvested for a period up to 12 h following ingestion of the drug. The levels of both the enantiomers were sustained for a period of 8 h (the plasma levels of d-methylphenidate were 8- to 10-fold higher than those of the l-enantiomer in the profiles of all six children). Mean areas under the plasma level time curves were 132.78 +/- 92.47 ng.h/mL for d-methylphenidate and 12.73 +/- 7.37 ng.h/mL for l-methylphenidate. The values of oral clearance and apparent volume of distribution calculated for l-enantiomer were higher than the corresponding values for the d-antipode.