Interactions in tissue distribution between methylphenidate and pemoline. II. Effects of methylphenidate or its metabolite on plasma and tissue concentrations of pemoline in the rat.

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Abstract
Interactions between methylphenidate (MPD) or its metabolite, ritalinic acid (RA), and pemoline in rats were investigated. At 20 min after intravenous administration of 3 mg/kg dose of pemoline as a loading dose, constant infusion at a rate of 139 .mu.g/h of the drug was carried out to give steady-state plasma level. In intravenous administration of 1 mg/kg dose of RA during the constant infusion of pemoline, the plasma concentration of pemoline before and after the administration of RA did not change. Steady-state pemoline also did not affect the pharmacokinetics of RA. On the other hand, in intravenous administration of 1 mg/kg dose of MPD during the constant infusion of pemoline, the plasma concentration of pemnoline slightly increased within 15 min after the administration of MPD. Thereafter the concentration of pemoline returned to the level before the superimposition of MPD within 60 min. The liver-, kidney-, lung-, muscle- and blood cell-to-plasma concentration ratios of pemoline at 5 min after the administration of MPD became smaller compared with those of pemoline in the absence of MPD, and those of pemoline at 60 min after the administration were approximately the same as those of pemoline in the absence of MPD. Steady-state pemoline did not affect the pharmacokinetics and tissue distribution of MPD. The increase of plasma concentration of pemoline caused by the superimposition of MPD may result in the displacement of pemoline from tissues and blood cell and/or MPD may inhibit the metabolism of pemoline.

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