Journal: Journal of pharmacokinetics and pharmacodynamics

Article Title: A Physiological Model of Granulopoiesis to Predict Clinical Drug Induced Neutropenia from in vitro Bone Marrow Studies: With Application to a Cell Cycle Inhibitor

doi: 10.1007/s10928-020-09680-6

Figure Lengend Snippet: Mechanism of action of palbociclib incorporated in the cell cycle model. Minus sign represents palbociclib inhibition of k1, plus sign represents palbociclib induction of the inactivation process.

Article Snippet: Palbociclib in vitro bone marrow assay Primary human bone marrow mononuclear cells (Lonza) were cultured in stemline II hematopoietic stem cell expansion medium (Sigma Aldrich), supplemented with 5% FBS and under induction by the following cytokines (R&D Systems): 25 ng/mL stem cell factor (SCF), 10 ng/mL G-CSF, 10 ng/mL granulocyte macrophage-colony stimulating factor, 3 U/mL erythropoietin (EPO), 15ng/mL thrombopoietin (TPO), 10ng/mL IL3, 10ng/mL IL6, and 25ng/mL Flt3 ligand.

Techniques: Inhibition

Journal: Journal of pharmacokinetics and pharmacodynamics

Article Title: A Physiological Model of Granulopoiesis to Predict Clinical Drug Induced Neutropenia from in vitro Bone Marrow Studies: With Application to a Cell Cycle Inhibitor

doi: 10.1007/s10928-020-09680-6

Figure Lengend Snippet: Palbociclib PK model parameter values (from [ 49 ]).

Article Snippet: Palbociclib in vitro bone marrow assay Primary human bone marrow mononuclear cells (Lonza) were cultured in stemline II hematopoietic stem cell expansion medium (Sigma Aldrich), supplemented with 5% FBS and under induction by the following cytokines (R&D Systems): 25 ng/mL stem cell factor (SCF), 10 ng/mL G-CSF, 10 ng/mL granulocyte macrophage-colony stimulating factor, 3 U/mL erythropoietin (EPO), 15ng/mL thrombopoietin (TPO), 10ng/mL IL3, 10ng/mL IL6, and 25ng/mL Flt3 ligand.

Techniques:

Journal: Journal of pharmacokinetics and pharmacodynamics

Article Title: A Physiological Model of Granulopoiesis to Predict Clinical Drug Induced Neutropenia from in vitro Bone Marrow Studies: With Application to a Cell Cycle Inhibitor

doi: 10.1007/s10928-020-09680-6

Figure Lengend Snippet: In vitro model results. Time course measurements for control (left panel) and all end-of-assay measurements (right panel) following palbociclib treatment. Symbol: measurements, lines: model predictions. Overall r2=0.94.

Article Snippet: Palbociclib in vitro bone marrow assay Primary human bone marrow mononuclear cells (Lonza) were cultured in stemline II hematopoietic stem cell expansion medium (Sigma Aldrich), supplemented with 5% FBS and under induction by the following cytokines (R&D Systems): 25 ng/mL stem cell factor (SCF), 10 ng/mL G-CSF, 10 ng/mL granulocyte macrophage-colony stimulating factor, 3 U/mL erythropoietin (EPO), 15ng/mL thrombopoietin (TPO), 10ng/mL IL3, 10ng/mL IL6, and 25ng/mL Flt3 ligand.

Techniques: In Vitro

Journal: Journal of pharmacokinetics and pharmacodynamics

Article Title: A Physiological Model of Granulopoiesis to Predict Clinical Drug Induced Neutropenia from in vitro Bone Marrow Studies: With Application to a Cell Cycle Inhibitor

doi: 10.1007/s10928-020-09680-6

Figure Lengend Snippet: Model parameter estimates from palbociclib in vitro bone marrow assay.

Article Snippet: Palbociclib in vitro bone marrow assay Primary human bone marrow mononuclear cells (Lonza) were cultured in stemline II hematopoietic stem cell expansion medium (Sigma Aldrich), supplemented with 5% FBS and under induction by the following cytokines (R&D Systems): 25 ng/mL stem cell factor (SCF), 10 ng/mL G-CSF, 10 ng/mL granulocyte macrophage-colony stimulating factor, 3 U/mL erythropoietin (EPO), 15ng/mL thrombopoietin (TPO), 10ng/mL IL3, 10ng/mL IL6, and 25ng/mL Flt3 ligand.

Techniques: In Vitro, Concentration Assay, Inhibition

Journal: Journal of pharmacokinetics and pharmacodynamics

Article Title: A Physiological Model of Granulopoiesis to Predict Clinical Drug Induced Neutropenia from in vitro Bone Marrow Studies: With Application to a Cell Cycle Inhibitor

doi: 10.1007/s10928-020-09680-6

Figure Lengend Snippet: Overall observed and model predicted number of patients that developed each grade of neutropenia in the palbociclib clinical trials (n=170).

Article Snippet: Palbociclib in vitro bone marrow assay Primary human bone marrow mononuclear cells (Lonza) were cultured in stemline II hematopoietic stem cell expansion medium (Sigma Aldrich), supplemented with 5% FBS and under induction by the following cytokines (R&D Systems): 25 ng/mL stem cell factor (SCF), 10 ng/mL G-CSF, 10 ng/mL granulocyte macrophage-colony stimulating factor, 3 U/mL erythropoietin (EPO), 15ng/mL thrombopoietin (TPO), 10ng/mL IL3, 10ng/mL IL6, and 25ng/mL Flt3 ligand.

Techniques: