Pharmacokinetic/Pharmacodynamic Analysis of Neutrophil Proliferation Induced by rhG-CSF in Patients Receiving Antineoplastic Drugs

Abstract

In the present study, we analyzed the eŠect of recombinant human granulocyte colony stimulating factor (rhG CSF) on neutrophil counts in cancer patients undergoing chemotherapy using a previously developed pharmacokinetic/ pharmacodynamic model. 7) The time proˆles of neutrophil counts in blood after repeated administration of rhG CSF to lung cancer patients undergoing chemotherapy could be analyzed by this model by considering the inhibition of neutrophil production by antineoplastic drugs. Although deviation was observed between the predicted and observed neutrophil counts in ovarian cancer patients, it may be possible to use this model for determining a rational dosage regimen of rhG CSF for patients undergoing chemotherapy.

Model-Based Approach to Describe G-CSF Effects in Carboplatin-Treated Cancer Patients

“…However, the adjunction of G-CSF as a "yes/no" covariate only provides an on/off switch and does not allow the prediction of more subtle adjustments in dose, dosing time and duration of G-CSF treatment. Other, more mechanistic models have been developed for that purpose (15,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) but some have been validated in very few cancer patients (26) or in healthy subjects only (22)(23)(24)28,29,31,32) or were not very physiological (15,30).…”

Comparison of the rapidity of onset of the therapeutic effect between nateglinide and mitiglinide by PK/PD analysis in rats

“…Considering the mechanism underlying the effect of both drugs, the receptor-binding-dissociation model was chosen as an optimal model. This model considers the rates of binding to a receptor and dissociation from a receptor Nakajima et al 1996;Sugiura et al 2004;Furuya et al 2007). An analysis employing the receptor-bindingdissociation model was performed, k on (second-order binding association constant to the receptor) and k off (firstorder dissociation constant from the receptor) were computed, and the rapidity of onset of the therapeutic effect was calculated by graphically representing and comparing the time-courses of changes in the receptor-binding rates for both drugs.…”