Predicting Resolvin D1 Pharmacokinetics in Humans with Physiologically‐Based Pharmacokinetic Modeling

Sjögren'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 that showed efficacy in preclinical models of SS. We developed a physiologically‐based pharmacokinetic (PBPK) model of R...

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Main Authors: Venkata K. Yellepeddi (Author), Kaustubh Parashar (Author), Spencer M. Dean (Author), Kevin M. Watt (Author), Jonathan E. Constance (Author), Olga J. Baker (Author)
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Published: Wiley, 2021-03-01T00:00:00Z.
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100 1 0 |a Venkata K. Yellepeddi  |e author 
700 1 0 |a Kaustubh Parashar  |e author 
700 1 0 |a Spencer M. Dean  |e author 
700 1 0 |a Kevin M. Watt  |e author 
700 1 0 |a Jonathan E. Constance  |e author 
700 1 0 |a Olga J. Baker  |e author 
245 0 0 |a Predicting Resolvin D1 Pharmacokinetics in Humans with Physiologically‐Based Pharmacokinetic Modeling 
260 |b Wiley,   |c 2021-03-01T00:00:00Z. 
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520 |a Sjögren'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 that showed efficacy in preclinical 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 (PK) 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 PKs. The PBPK model adequately captured the observed concentrations of RvD1 administered at different doses and in different species. The PKs 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. 
546 |a EN 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
690 |a Public aspects of medicine 
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786 0 |n Clinical and Translational Science, Vol 14, Iss 2, Pp 683-691 (2021) 
787 0 |n https://doi.org/10.1111/cts.12930 
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787 0 |n https://doaj.org/toc/1752-8062 
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