{"doi":"10.33552/appr.2020.02.000545","title":"PBPK Models of Two CNS Stimulants, Amphetamine and Methylphenidate, for Clinical Dosing Regimen Optimizations","abstract":"Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disease. Amphetamine (AMP) based and methylphenidate (MPH)- based agents are the first-line medications that are used as the treatment for ADHD. In this study, we successfully constructed and validated Physiologically based Pharmacokinetic (PBPK) models for AMP of oral extended-release formation and MPH of oral immediate-release formulation and predicted the toxic and lethal doses for these two medications using our PBPK models. To create the models, we utilized drug-related parameters and system-related parameters that are obtained from database, ADMET Predictor, Simcyp built-in predictor and literature. Overall, the predicted AMP concentration in plasma was slightly underestimated but is still located within the confidence interval, while our PBPK model for MPH can predict the PK profiles very well according to the clinical data, indicating the credibility of our model. We also stated that with the application of our PBPK models, we can effectively design more rational drug regimen and estimate the toxic risk under different doses. In terms of our simulation results, we also concluded that the toxic dose of sustained-release AMP is approximately 100-400mg, and the dose over 400mg may even cause death. The dosage that is over 300mg is strongly not recommended. As for immediate-release oral MPH, the maximal recommended dose is also 100mg.","journal":"Archives of Pharmacy & Pharmacology Research","year":2020,"id":144854,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9166,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":86256,"name":"Junmei Wang","orcid":"0000-0002-9607-8229","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:48.191325Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}