Dataset Information

The interaction between prognostic and pharmacodynamic biomarkers.

ABSTRACT:

Background

Interactions between prognostic and pharmacodynamic (PD) biomarkers have received little attention.

Methods

Prognostic and PD utilities were assessed with linear mixed-effects models using published data on repeated measurements of circulating caspase-cleaved (ctCK18) and total (tCK18) cytokeratin 18, in 57 patients with metastatic colorectal cancer undergoing chemotherapy.

Results

The model for tCK18 (but not cCK18) separated the prognostic/PD interaction from the pure prognostic effect, illustrating the principle of dual prognostic and PD characteristics for a given biomarker.

Conclusion

These models provide the framework for the analysis and interpretation of longitudinal data to detect prognostic/PD biomarker interactions.

SUBMITTER: Bouranis L

PROVIDER: S-EPMC3790178 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Publications

The interaction between prognostic and pharmacodynamic biomarkers.

Bouranis L L Sperrin M M Greystoke A A Dive C C Renehan A G AG

British journal of cancer 20130903 7

<h4>Background</h4>Interactions between prognostic and pharmacodynamic (PD) biomarkers have received little attention.<h4>Methods</h4>Prognostic and PD utilities were assessed with linear mixed-effects models using published data on repeated measurements of circulating caspase-cleaved (ctCK18) and total (tCK18) cytokeratin 18, in 57 patients with metastatic colorectal cancer undergoing chemotherapy.<h4>Results</h4>The model for tCK18 (but not cCK18) separated the prognostic/PD interaction from t ...[more]

PMID: 24002599

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Project description:Background and objectiveRosuvastatin and ezetimibe are commonly applied in lipid-lowering pharmacotherapy. However, the pharmacokinetic (PK) interaction was not clear by the coadministration of rosuvastatin and ezetimibe. This study investigated the pharmacodynamic (PD) and PK interactions between rosuvastatin and ezetimibe through a crossover clinical trial.Subjects and methodsA randomized, open-label, multiple-dose, two-treatment, two-period, two-sequence crossover study with two treatment parts was conducted in healthy male subjects. Study part A involved rosuvastatin, and study part B involved ezetimibe. A total of 25 subjects in both parts completed the PK and PD evaluations. Rosuvastatin (20 mg) or ezetimibe (10 mg) was administered once daily for 7 days as monotherapy or co-therapy. The plasma concentrations of rosuvastatin, total ezetimibe and free ezetimibe were measured for 72 h after day 7. Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) were investigated for the PD assessments on day 1 (pretreatment) and day 8.ResultsRosuvastatin and ezetimibe presented multiple peaks. The 90% confidence intervals (CIs) of the geometric mean ratios for the peak plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve during the dosing interval at steady state (AUCτ,ss) of rosuvastatin and total ezetimibe were within the range 0.8-1.25. However, the coadministration increased the systemic exposure of free ezetimibe. In the PD assessments, rosuvastatin and ezetimibe monotherapy reduced the LDL-C and TC levels effectively. In addition, the lipid-lowering effects of the coadministration corresponded to an approximate summation of the effects of rosuvastatin and ezetimibe monotherapy. However, no significant changes in HDL-C were observed with rosuvastatin or ezetimibe treatment. No significant safety issue was noted.ConclusionThe coadministration of rosuvastatin and ezetimibe revealed a bioequivalent PK interaction. Additional lipid-lowering effects, including decreased LDL-C and TC, were observed as expected in combination therapy without significant safety concern.

Dataset Information

The interaction between prognostic and pharmacodynamic biomarkers.

Background

Methods

Results

Conclusion

Publications

The interaction between prognostic and pharmacodynamic biomarkers.

Similar Datasets

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