Impaired hepatic bile acid export may contribute to development of cholestatic drug-induced liver injury (DILI). The multidrug resistance-associated proteins (MRP) 3 and 4 are postulated be compensatory basolateral efflux transporters when biliary excretion by the salt pump (BSEP) is impaired. BSEP inhibition a risk factor for DILI. This study aimed characterize relationship between MRP3, MRP4, potential drugs. inhibitory effect 88 drugs (100 <i>μ</i>M) on MRP3- MRP4-mediated substrate...

To assess circulating biomarkers as predictors of antitumor response to atezolizumab (anti-programmed death-ligand 1 (PD-L1), Tecentriq) serum pharmacokinetic (PK) and 95 plasma were analyzed in 88 patients with relapsed/refractory non-small cell lung cancer (NSCLC) receiving i.v. q3w (10-20 mg/kg) the PCD4989g phase I clinical trial. Following exploratory analyses, two chosen for further study correlation change tumor size (the sum longest diameter) was assessed a...

Early identification of patients with febrile neutropenia (FN) is desirable for initiation preventive treatment, such as antibiotics. In this study, the time courses two inflammation biomarkers, interleukin (IL)-6 and C-reactive protein (CRP), following adjuvant chemotherapy breast cancer, were characterized. The potential to predict development FN by IL-6 CRP, other model-derived clinical variables, was explored.The CRP in cycles 1 4 cancer treatment described turnover models where...

The large heterogeneity in response to immune checkpoint inhibitors is driving the exploration of predictive biomarkers identify patients who will respond such treatment. We extended our previously suggested modeling framework atezolizumab pharmacokinetics, IL18, and tumor size (TS) dynamics, also include overall survival (OS). Baseline model‐derived variables were explored as predictors OS 88 with non‐small cell lung cancer treated atezolizumab. To investigate impact follow‐up length on...

Abstract Purpose: Quantitative relationships between treatment-induced changes in tumor size and circulating cell (CTC) counts, their links to overall survival (OS), are lacking. We present a population modeling framework identifying quantifying such relationships, based on longitudinal data collected patients with metastatic colorectal cancer (mCRC) evaluate the value of CTC counts as predictors OS. Experimental Design: A pharmacometric approach (i.e., pharmacodynamic modeling) was used...

&lt;p&gt;Baseline characteristics of the 451 patients included in analysis data set&lt;/p&gt;

&lt;p&gt;VPC of the tumor size model taking dropout into account. The solid and dashed lines in left panel represent observed median 5th (lower line) 95th (upper percentiles data, respectively. shaded areas are corresponding 95% CIs simulated derived from 200 simulations final model. grey horizontal line represents SLD 10 mm.&lt;/p&gt;

&lt;p&gt;KMMC VPCs of the base (top plots) and final (bottom OS model. The observed mean BTS age (black lines), in comparison to 95% CI based on 100 simulations from models (shaded areas), patients remaining study over time are illustrated left right plots, respectively. Vertical lines indicate censored events.&lt;/p&gt;

&lt;p&gt;Supplementary Methods&lt;/p&gt;

&lt;p&gt;Summary of number patients and reasons for exclusion from the analysis data set.&lt;/p&gt;

&lt;div&gt;AbstractPurpose:&lt;p&gt;Quantitative relationships between treatment-induced changes in tumor size and circulating cell (CTC) counts, their links to overall survival (OS), are lacking. We present a population modeling framework identifying quantifying such relationships, based on longitudinal data collected patients with metastatic colorectal cancer (mCRC) evaluate the value of CTC counts as predictors OS.&lt;/p&gt;Experimental Design:&lt;p&gt;A pharmacometric approach (i.e.,...

&lt;div&gt;AbstractPurpose:&lt;p&gt;Quantitative relationships between treatment-induced changes in tumor size and circulating cell (CTC) counts, their links to overall survival (OS), are lacking. We present a population modeling framework identifying quantifying such relationships, based on longitudinal data collected patients with metastatic colorectal cancer (mCRC) evaluate the value of CTC counts as predictors OS.&lt;/p&gt;Experimental Design:&lt;p&gt;A pharmacometric approach (i.e.,...

&lt;p&gt;VPC of the proportions CTC count equal to 0, 1, 2, 3, &gt;3 and {less than or to}5, &gt;5 to}10, &gt;10 to}50, &gt;500 to}100 &gt;100 over time in final model. The dots represent observed (connected with a line) shaded areas are 95% CI simulated data, derived from 200 simulations model.&lt;/p&gt;

&lt;p&gt;Schematic representation of the tumor size model. The total SLD is a sum all compartments in pink (drug sensitive fraction) and orange resistant boxes.&lt;/p&gt;

&lt;p&gt;Individual tumor size predictions in the final model (lines) and observed sizes (dots) for 9 example patients (indicated by shape of dots), 3 each subpopulation.&lt;/p&gt;

&lt;p&gt;Î"OFV for the explored drop-out predictors in first step&lt;/p&gt;

&lt;p&gt;VPC of the tumor size model taking dropout into account. The solid and dashed lines in left panel represent observed median 5th (lower line) 95th (upper percentiles data, respectively. shaded areas are corresponding 95% CIs simulated derived from 200 simulations final model. grey horizontal line represents SLD 10 mm.&lt;/p&gt;

&lt;p&gt;Supplementary Methods&lt;/p&gt;

&lt;p&gt;Î"OFV for the explored drop-out predictors in first step&lt;/p&gt;

&lt;p&gt;Individual tumor size predictions in the final model (lines) and observed sizes (dots) for 9 example patients (indicated by shape of dots), 3 each subpopulation.&lt;/p&gt;

&lt;p&gt;VPC of the proportions CTC count equal to 0, 1, 2, 3, &gt;3 and {less than or to}5, &gt;5 to}10, &gt;10 to}50, &gt;500 to}100 &gt;100 over time in final model. The dots represent observed (connected with a line) shaded areas are 95% CI simulated data, derived from 200 simulations model.&lt;/p&gt;

&lt;p&gt;Summary of number patients and reasons for exclusion from the analysis data set.&lt;/p&gt;

&lt;p&gt;Schematic representation of the tumor size model. The total SLD is a sum all compartments in pink (drug sensitive fraction) and orange resistant boxes.&lt;/p&gt;