A Bayesian population PK–PD model for ispinesib/docetaxel combination-induced myelosuppression

Abstract

The PK/PD model developed for ispinesib/docetaxel, may be used to examine different schedules, doses, and infusion times of both agents. Bayesian methods allow for the use of prior information available for the model parameters.

Evaluation of 4β‐Hydroxycholesterol as a Clinical Biomarker of CYP3A4 Drug Interactions Using a Bayesian Mechanism–Based Pharmacometric Model

“…The Bayesian approach is more commonly applied in toxicology research, in which the algorithms and software available to implement such approaches have been widely adopted 12 , 13 . However, examples of more clinically oriented PK/PD models developed using Bayesian approaches have also been reported 14 , 15 , 16 . MCMC Bayesian algorithms offer distinct advantages over more commonly used deterministic estimation algorithms.…”

A simultaneous analysis of the time-course of leukocytes and neutrophils following docetaxel administration using a semi-mechanistic myelosuppression model

“…This model has since the original publication been successfully applied to both leukocyte and neutrophil measurements following several additional anti-cancer drugs and regimens [6][7][8][9][10][11][12][13][14][15][16]. It has also been shown to satisfactorily describe thrombocyte and lymphocyte measurements following chemotherapy [17][18][19].…”

“…Proposed alterations of the model structure include a log-linear drug effect model instead of a linear or Emax model [10], an addition of an effect delay compartment to account for the distribution of drug from the plasma to the bone marrow [10] and an addition of a neutrophil pool to describe an early increase of neutrophil count after dosage [20]. The model has further been extended to describe the combined drug effect following combination therapy of anticancer drugs [13,17,18,[21][22][23][24], to incorporate the effect of administrated exogenous G-CSF [22,25,26] and to capture the time-course of neutrophils following peripheral blood stem-cell transplantation [26]. Additionally covariates [6,9,10,20,[27][28][29][30] and inter-occasion variability [16] have been explored using the model.…”

Population pharmacokinetic–pharmacodynamic modelling and simulation of neutropenia induced by TP300, a novel topoisomerase I inhibitor

“…Drug‐related parameters then quantify the anti‐proliferative effect of a cytotoxic drug on the bone marrow . This model has shown broad utility in relating changes in neutrophil counts to pharmacokinetics, and has been applied to many single‐agent and combination regimens including irinotecan …”