Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: Mathematical modelling guides dose optimisation to minimise neutropenia

Closed form solutions and dominant elimination pathways of simultaneous first-order and Michaelis–Menten kinetics

“…Figure 6(a) indicates a case of dominance of linear elimination where CL l [ CL int , in which we can see that the concentration time curve with linear elimination alone is close to that of simultaneous model (Eqs. [1][2]. This behavior is in fact independent of the initial dose.…”

“…Substances that manifest parallel elimination mechanisms are not rare, including growth factors and ethanol [1][2][3][4][5]. Their elimination generally involves a linear elimination through organs (kidney, lung, skin, etc.…”

“…), combined simultaneously with a non-linear elimination that metabolizes and clears the parent products. This kind of elimination kinetics are typically exhibited by hormone drugs, such as granulocyte colony-stimulating factor (G-CSF), which are used in combination with chemotherapeutic agents to stimulate the production of hematopietic cells when their number is reduced [1][2][3][4]. While several models of these kinetics have been reported, their systematic analysis allowing for a quantitative characterization of the interaction between these two elimination pathways is still lacking.…”

Blood Cell Dynamics: Half of a Century of Modelling

“…Most of the published works of the beginning of this decade are in the continuity of the end of the 2000's: cyclical neutropenia treatment by G-CSF [181], [182], [71], [94], [301], CML study [139], [158], [224], [106], [48], [178], [257], AML study [275], [274], [47], granulopoiesis [262], [263], HSC study [234], [207], [277], [33], [276], [281], [218], [5], [18], [136], [74] (with two nice reviews dealing with treatments of hematological diseases [96]), [294], very few on erythropoiesis [90], [261], [68] megakaryopoiesis [269], cell fate analysis [219]. There were mathematical development of structured populations [70], [111], [67], [114] with delay equations [20], [88], [21], [15], [59], [4], …”

Approaching Pharmacometrics as a Paleontologist Would: Recovering the Links Between Drugs and the Body Through Reconstruction

“…Further, as is the case with the more common physiologically based pharmacokinetic model, the role of PK and PD variability upon system‐level models has not been fully addressed . In response, using a physiological model of granulopoiesis that we developed for the optimization of chemotherapy, we have recently shown that when the physiology is sufficiently detailed, the model inherently explains and reduces the previously estimated population PK variability . This is likely attributable to its bottom‐up construction because development from first principles suggests that variability is explicated and incorporated into the minute details of the resulting models and their parameters .…”