Predicting Resolvin D1 Pharmacokinetics in Humans with Physiologically‐Based Pharmacokinetic Modeling
| Autor: | Spencer M. Dean, Kevin M. Watt, Jonathan E. Constance, Olga J. Baker, Venkata K. Yellepeddi, Kaustubh Parashar |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Physiologically based pharmacokinetic modelling Docosahexaenoic Acids Pharmacokinetic modeling Drug Evaluation Preclinical Datasets as Topic Pharmacology Models Biological Salivary Glands Article General Biochemistry Genetics and Molecular Biology Mice Pharmacokinetics Quantitative pharmacology Animals Humans Medicine Effective treatment Tissue Distribution General Pharmacology Toxicology and Pharmaceutics Dose-Response Relationship Drug business.industry Research lcsh:Public aspects of medicine General Neuroscience lcsh:RM1-950 lcsh:RA1-1270 Articles General Medicine Resolvin d1 Sjogren's Syndrome lcsh:Therapeutics. Pharmacology Models Animal Female business |
| Zdroj: | Clinical and Translational Science, Vol 14, Iss 2, Pp 683-691 (2021) Clinical and Translational Science |
| ISSN: | 1752-8062 1752-8054 |
| DOI: | 10.1111/cts.12930 |
| Popis: | Sjogren's syndrome (SS) is an autoimmune disease with no effective treatment options. Resolvin D1 (RvD1) belongs to a class of lipid-based specialized pro-resolving mediators (SPM's) that showed efficacy in pre-clinical models of SS. We developed a physiologically based pharmacokinetic (PBPK) model of RvD1 in mice and optimized the model using plasma and salivary gland pharmacokinetic studies performed in NOD/ ShiLtJ mice with SS-like features. The predictive performance of the PBPK model was also evaluated with two external datasets from the literature reporting RvD1 pharmacokinetics. The PBPK model adequately captured the observed concentrations of RvD1 administered at different doses and in different species. The pharmacokinetics of RvD1 in virtual humans were predicted using the verified PBPK model at various doses (0.01 - 10 mg/kg). The first-in-human predictions of RvD1 will be useful for the clinical trial design and translation of RvD1 as an effective treatment strategy for SS. |
| Databáze: | OpenAIRE |
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