Importance of pharmacokinetic profile and timing of coadministration of short- and long-acting formulations of methylphenidate on patterns of subjective responses and abuse potential

Objective: Subjective responses (ie, liking, disliking) to stimulants are thought to be proxies for abuse potential. Greater subjective responses have been documented in formulations that are more rapidly absorbed. However, repeat dosing has not been examined. Methods: Subjective responses on the Drug Rating Questionnaire were compared in 26 healthy adults after administration of short- (immediate-release [IR] methylphenidate [MPH]) and long- (osmotically controlled-release oral delivery system [OROS] MPH) acting stimulant formulations. The second dose was administered 4 hours after initial dosing. All subjects received all 5 conditions (ie, placebo to placebo; IR-MPH to IR-MPH; IR-MPH to OROS-MPH; OROS-MPH to IR-MPH; or OROS-MPH to OROS-MPH) in a double-blind, counter-balanced design on 5 separate days. Results: Plasma levels and subjective patterns of detection were higher when an IR formulation was administered during the ascending phase of a first-administered longacting dose (OROS). Conclusion: These results emphasize the critical role that formulation type (IR vs OROS) and timing of administration (ascending vs descending phase) play when short- and long-acting formulations are coadministered. Such knowledge provides important information for clinicians about the safety and tolerability of the timing of repeat dosing of various permutations of coadministration of MPH formulations.