Fed and Fasted Administration of a Novel Extended‐Release Methylphenidate Orally Disintegrating Tablet Formulation for the Treatment of ADHD

Abstract

Extended-release methylphenidate is a first-line treatment for attention-deficit/hyperactivity disorder. A methylphenidate extended-release orally disintegrating tablet (MPH XR-ODT) has recently been developed. Here we report an open-label, randomized, 2-period, 2-treatment crossover study to determine the effect of food on the bioavailability of a single 60-mg dose of MPH XR-ODT in healthy adults. Blood samples were collected predose through 36 hours postdose. Maximum plasma concentration (C ), time to maximum plasma concentration (T ), terminal elimination half-life (T ), overall systemic exposure (AUC and AUC ), and partial areas under the concentration curve (AUC , AUC , and AUC ) were calculated. In total, 48 participants completed the study. For total methylphenidate from MPH XR-ODT, the lower limit of the 90% confidence interval (CI) around the geometric mean ratio (GMR, fed/fasted) for C was below 80%, indicating a slightly decreased rate of absorption with food, whereas the 90%CIs around the GMRs of AUC and AUC were within the 80%-125% limits, suggesting no food effect on exposure. The most common adverse events (AEs) were palpitations and decreased appetite. No serious, unusual, or unexpected AEs were reported. Thus, food had no substantial effect on overall bioavailability of MPH XR-ODT, which may be an important factor for some patients.

pH-dependent spontaneous hydrolysis rather than gut bacterial metabolism reduces levels of the ADHD treatment, Methylphenidate

“…Preventing MPH from reaching an increased pH in the ileum by taking the medication under fasting conditions could improve its bioavailability, as MPH would be absorbed higher up in the small intestine where a pH below 7 should limit the non-enzymatic hydrolysis to around 10% (Fig 3A). Reports on the pharmacokinetics of MPH comparing fed and fasting conditions are scarce and reveal contradictory results [31,32]. Although food intake tends to increase luminal pH of the gut [33], not enough information is available regarding the pH levels in the small intestine in fed or fasting conditions and how this could affect the bioavailability of MPH.…”

Stability of Methylphenidate under Various pH Conditions in the Presence or Absence of Gut Microbiota

“…Preventing MPH from reaching an increased pH in the ileum by taking the medication under fasting conditions could improve its bioavailability, as MPH would be absorbed higher up in the small intestine [12], where a pH below 7 should limit the non-enzymatic hydrolysis to around 10% (Figure 3A). Reports on the pharmacokinetics of MPH comparing fed and fasting conditions are scarce and reveal contradictory results [35,36].…”