Pharmacokinetic Modeling

Pharmacokinetic Modeling

In vitro Cytotoxicity and Pharmacokinetic Evaluation of Pharmacological Ascorbate in Dogs

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In vitro Cytotoxicity and Pharmacokinetic Evaluation of Pharmacological Ascorbate in Dogs

High-dose, pharmacological ascorbate (P-AscH−) is preferentially cytotoxic to human cancer cells in vitro. Investigations on the efficacy of P-AscH− as an adjuvant treatment for multiple human cancers are on-going, but has yet to be formally investigated in dogs. The primary objectives of this study were to determine the pharmacokinetic (PK) profile of P-AscH− in healthy Beagle dogs and the effects of P-AscH− on canine osteosarcoma cells in vitro.

Musser ML, Mahaffey AL, Fath MA, Buettner GR, Wagner BA, Schneider BK, et al. In vitro Cytotoxicity and Pharmacokinetic Evaluation of Pharmacological Ascorbate in Dogs. Front Vet Sci [Internet]. 2019 [cited 2020 May 29];6. Available from: https://www.frontiersin.org/articles/10.3389/fvets.2019.00385/full

Pharmacodynamic Modeling, Pharmacokinetic Modeling

Optimal Scheduling of First-Line Therapeutics in Non-Small Cell Lung Cancer

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Optimal Scheduling of First-Line Therapeutics in Non-Small Cell Lung Cancer

In the United States, lung cancer causes more deaths per year (135,720 estimated for 2020) than does any other type of cancer, and 84% of lung cancer deaths are caused by non-small cell lung cancer (NSCLC) (Siegel et al., 2020). Treatment for NSCLC has expanded from a limited set of chemotherapeutics and surgery to include immunotherapy, radiotherapy, targeted adjunct therapy, and immune checkpoint inhibitors (Jászai & Schmidt, 2019; Liu et al., 2017). Between 1996 and 2010, it’s estimated that the percentage of NSCLC patients receiving some combination of targeted therapy and chemotherapy has increased by 20% for stage I/II patients, 28% for stage IIIA patients, and at least 15% for stage IIIB/IV patients (Kaniski et al., 2017). Parallel with the advancements in treatments, the prognosis for these patients has also been improving. The 5-year survival rate in NSCLC has advanced from 10.7% in 1973 to slightly less than 21% as of 2019 (Lu et al., 2019). Today, a combination of chemotherapy (including platinum-based doublets), immune checkpoint inhibitors (e.g. PD-1/PD-L1), and antiangiogenics (e.g. bevacizumab) is recommended as first-line therapy for the management of metastatic or recurrent NSCLC (Lung Cancer – Non-Small Cell – Types of Treatment, 2012). (more…)

Pharmacokinetic Modeling

Undersampling Bias on Cmax and Tmax Estimation

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Undersampling Bias on Cmax and Tmax Estimation

In Pharmacokinetic studies, researchers use a controlled research environment to determine the biological fate of a pharmaceutical after administration. In practice, this means determining the typical plasma concentration of the drug from the moment of administration until effective elimination of the drug from the body. From this typical profile, researchers can predict useful clinical metrics like the predicted maximum concentration (Cmax) of the pharmaceutical and the time it takes for the drug to reach peak plasma concentration (Tmax ) after administration. (more…)

Pharmacokinetic Modeling

Nonlinear Mixed-Effects Pharmacokinetic Modeling of the Novel COX-2 Selective Inhibitor Vitacoxib in Dogs

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Nonlinear Mixed-Effects Pharmacokinetic Modeling of the Novel COX-2 Selective Inhibitor Vitacoxib in Dogs

In this manuscript, we use a nonlinear mixed effects (NLME) framework to develop a compartmental model of vitacoxib disposition kinetics in dogs after intravenous (I.V), oral (P.O) and subcutaneous (S.C) dosing. The influence of age, sex, bodyweight and food intake were evaluated as covariates on model parameters to assess the need for dose adjustment of vitacoxib in dogs.

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