ArticlePharmaceutics2020
Physiologically Based Pharmacokinetic Modeling of Transdermal Selegiline and Its Metabolites for the Evaluation of Disposition Differences between Healthy and Special Populations.
Article in Pharmaceutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 33 citations in OpenAlex.
- Skin physiologically based pharmacokinetic modeling: current research progress, software comparison, and future perspectives.Drug delivery · 2026Review
- Topical selegiline accelerates cutaneous wound healing with phase-specific modulation of MAPK signaling.Inflammopharmacology · 2026Article
- Physiologically Based Pharmacokinetic Modeling for Predicting Drug Levels After Bariatric Surgery: Vardenafil Exposure Before vs. After Gastric Sleeve/Bypass.Biomolecules · 2025Article
- Erectile Dysfunction Therapy of Bariatric Patients: Tadalafil Biopharmaceutics and Pharmacokinetics Before vs. After Gastric Sleeve/Bypass.The AAPS journal · 2024Article
- The Complexity of Bariatric Patient's Pharmacotherapy: Sildenafil Biopharmaceutics and Pharmacokinetics before vs. after Gastric Sleeve/Bypass.Pharmaceutics · 2023Article
- Assessing Dose-Exposure-Response Relationships of Miltefosine in Adults and Children using Physiologically-Based Pharmacokinetic Modeling Approach.Pharmaceutical research · 2023Article
- Mechanistic modeling of drug products applied to the skin: A workshop summary report.CPT: pharmacometrics & systems pharmacology · 2023Review
- Multi-phase multi-layer mechanistic dermal absorption (MPML MechDermA) model to predict local and systemic exposure of drug products applied on skin.CPT: pharmacometrics & systems pharmacology · 2022Article
- Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution.Pharmaceutics · 2022Article
- Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK.Frontiers in pharmacology · 2022Article
- Skin-on-a-Chip Technology for Testing Transdermal Drug Delivery-Starting Points and Recent Developments.Pharmaceutics · 2021Review
- Physiologically-based pharmacokinetic modeling to support bioequivalence and approval of generic products: A case for diclofenac sodium topical gel, 1.CPT: pharmacometrics & systems pharmacology · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A physiologically based pharmacokinetic (PBPK) model of selegiline (SEL), and its metabolites, was developed in silico to evaluate the disposition differences between healthy and special populations. SEL is metabolized to methamphetamine (MAP) and desmethyl selegiline (DMS) by several CYP enzymes. CYP2D6 metabolizes the conversion of MAP to amphetamine (AMP), while CYP2B6 and CYP3A4 predominantly mediate the conversion of DMS to AMP. The overall prediction error in simulated PK, using the developed PBPK model, was within 0.5-1.5-fold after intravenous and transdermal dosing in healthy and elderly populations. Simulation results generated in the special populations demonstrated that a decrease in cardiac output is a potential covariate that affects the SEL exposure in renally impaired (RI) and hepatic impaired (HI) subjects. A decrease in CYP2D6 levels increased the systemic exposure of MAP. DMS exposure increased due to a reduction in the abundance of CYP2B6 and CYP3A4 in RI and HI subjects. In addition, an increase in the exposure of the primary metabolites decreased the exposure of AMP. No significant difference between the adult and adolescent populations, in terms of PK, were observed. The current PBPK model predictions indicate that subjects with HI or RI may require closer clinical monitoring to identify any untoward effects associated with the administration of transdermal SEL patch.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.