#Nonmem pd time course software
NONMEM software was used to perform the modeling and simulation analyses. The model was qualified and simulations were undertaken to evaluate the neutropenia schedule dependency and the effects of selected covariates.
![nonmem pd time course nonmem pd time course](https://www.researchgate.net/profile/Sonia_Khier/publication/342154899/figure/fig5/AS:961842037940226@1606332420186/Example-of-codes-of-a-NONMEM-control-file-for-implementation-of-PRIOR-NWPRI-subroutine.png)
A first-order process quantified by the rate constant k(e0) described the trabectedin concentrations at the effect compartment (C(e)), which were assumed to reduce the proliferation rate and/or to increase the killing rate of the progenitor cells according to the function alphaC(e)beta. The model estimated three system-related parameters: ANC at baseline (Circ0), mean transit time in bone marrow (MTT), and a feedback parameter (gamma). To capture the rebound effect due to endogenous growth factors, the model included a feedback mechanism. The PK/PD model comprised a trabectedin-sensitive progenitor cell compartment, linked to the peripheral blood compartment, through three transition compartments representing the maturation chain in the bone marrow. Data from 699 patients who received intravenous trabectedin as monotherapy (dose range: 0.006-1.8 mg/m2) as a 1-, 3-, or 24-h infusion every 21 days 1- or 3-h infusion on days 1, 8, and 15 every 28 days or a 1-h infusion daily for 5 consecutive days every 21 days were used to develop (N=405 ANCs=7,291) and validate (N=294 ANCs=5,029) the model.
![nonmem pd time course nonmem pd time course](https://d3i71xaburhd42.cloudfront.net/25169ec53d306b4f7549057ecf85a51fe2a6f67e/6-Figure1-1.png)
Our objective was to develop a pharmacokinetic-pharmacodynamic (PK/PD) model that describes the time course of the absolute neutrophil counts (ANCs) in cancer patients receiving trabectedin. Myelosuppression was found to be one of the main toxicities of trabectedin (ET-743, Yondelis) during phase I/II studies.