ArticlePharmaceutical research2013
Use of partial AUC (PAUC) to evaluate bioequivalence--a case study with complex absorption: methylphenidate.
Article in Pharmaceutical research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed.
- Ethanol Interactions With Dexmethylphenidate and dl-Methylphenidate Spheroidal Oral Drug Absorption Systems in Healthy Volunteers.Journal of clinical psychopharmacology · 2017Trial
- Single-dose pharmacokinetics of methylphenidate extended-release multiple layer beads administered as intact capsule or sprinkles versus methylphenidate immediate-release tablets (Ritalin(®)) in healthy adult volunteers.Journal of child and adolescent psychopharmacology · 2014Trial
- Impact of release mechanism on the pharmacokinetic performance of PAUC metrics for three methylphenidate products with complex absorption.Pharmaceutical research · 2014Trial
- Mechanism-based classification of in vitro-in vivo correlation failures and model-informed strategies for drug product development.Archives of pharmacal research · 2026Review
- Partial Area Under the Curve: A Revelatory Story in Pharmacokinetics.Clinical pharmacokinetics · 2026Review
- The First Physiologically Based Pharmacokinetic (PBPK) Model for an Oral Vaccine Using Alpha-Tocopherol as an Adjuvant.Pharmaceutics · 2023Article
- Investigation of the Discriminatory Ability of Pharmacokinetic Metrics for the Bioequivalence Assessment of PEGylated Liposomal Doxorubicin.Pharmaceutical research · 2018Article
- The Two Main Goals of Bioequivalence Studies.The AAPS journal · 2017Article
- Population pharmacokinetics of methylphenidate hydrochloride extended-release multiple-layer beads in pediatric subjects with attention deficit hyperactivity disorder.Drug design, development and therapy · 2015Article
- Quantitative Characterization of the Smoothness of Extended-release Methylphenidate Pharmacokinetic Profiles.Innovations in clinical neuroscienceArticle
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMethylphenidate modified-release products produce early and late peak concentrations critical for treatment of morning and afternoon symptoms of attention deficit hyperactivity disorder (ADHD). Standard bioequivalence (BE) criteria cannot be applied to these products. The performance of partial area under the drug concentration-time curve (PAUC), Cmax and AUCINF to assess BE were independently evaluated for two products.
methodsA two-stage analysis was performed on plasma data for two methylphenidate modified-release products (Product 1 and 2). Simulations using the fitted parameters determined how changes in fast absorption rate constant (K0Fast) and fraction available (F1) affected curve shape and BE determination using Cmax, AUCINF and PAUC.
resultsThe sensitivity of the mean PAUC(test)/PAUC(reference) ratios to changes in K0Fast(test) are product dependent. Product 1 mean PAUC(test)/PAUC(reference) ratios for PAUC0-4h are more responsive to both decreases and increases in K0Fast(test) than Product 2. Product 2 showed a greater response in the mean PAUC(test)/PAUC(reference) ratio for PAUC0-4h when the K0Fast(test) is decreased and less response as the value is increased.
conclusionsPAUC estimated curve shape is sensitive to changes in absorption and are product specific, and may require a new PAUC metric for each drug. A non-product specific metric to assess curve shape is warranted.
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