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For pharmacokinetic and practical reasons, methylphenidate (MPH) for the treatment of attention-deficit/hyperactivity disorder (ADHD) is predominantly prescribed in biphasic release dosage forms. The aim of this work is the presentation and discussion of the pharmacokinetics of the new preparation Methysym®. The pharmacokinetics of Methysym® were investigated in 24 healthy volunteers in a bioequivalence study with Equasym® Retard as comparator. The methodology conformed to customary regulatory standards, supplemented by the evaluation of partial pharmacokinetic parameters for biphasic systems. In a post-hoc analysis, a model-independent estimation of the shape of individual plasma concentration-time curves was also performed. Bimodal profiles were accepted only when the zeros of a numerical first derivative of smoothed plasma concentration-time curves sufficiently suggested the existence of a minimum. As a result, Methysym® and Equasym® were found to be bioequivalent according to regulatory criteria with, for example, (geometric means in each case) AUC0-∞ = 78.2 (ng/ml) × h (Methysym®), AUC0-∞ = 75.7 (ng/ml) × h (Equasym®) and a point estimator Methysym®/Equasym® = 103.2% (90% confidence interval 100.4%–106.2%) for the 30 mg dose. MPH exposure as AUC0-∞ can differ interindividually by up to 3.5-fold for the same preparation. After fasting administration of Methysym®, plasma concentration-time curves were bimodal in 20 subjects (83.3%) versus nine subjects (37.5%) after administration of Equasym® (p = 0.003). In the subgroup of subjects with bimodal plasma concentration-time curves, the percentage ratio of plasma concentrations at the first and second maximum was significantly smaller for Methysym® than for Equasym® (74.6% ± 14.4% vs. 104.2% ± 13.4%, arithmetic means ± standard deviation, p < 0.001). It is concluded that Methysym® releases biphasically over a mid-range duration and is bioequivalent to Equasym®. This allows to infer of an overall comparable efficacy to Equasym®. Due to its particular galenic design, Methysym® has a distinct plasma concentration profile with a high proportion of subjects exhibiting a bimodal course of the plasma concentration-time curve. *Online only English version. The German print version is published as an Original Paper in: Psychopharmakotherapie. 2025;32(05):181–190 (DOI: 10.52778/ppt20250015)