Pro-inflammatory cytokines, which are elevated in pro-inflammatory disease states (e.g., type II diabetes mellitus \[T2DM\], irritable bowel diseases \[IBD\], and end stage renal disease \[ESRD\]) have been shown to inhibit hepatic drug-metabolizing enzymes, including members of the cytochrome P450 (CYP) family, and drug transporters; resultantly, pro-inflammatory diseases have been demonstrated to increase the exposure and potential for adverse drug events with co-administered CYP and drug transporter substrates. However, the clinical relevance of pro-inflammatory disease-drug interactions has not been systematically evaluated. The long-term goal of this research is to establish clinical strategies to mitigate pro-inflammatory disease-drug interactions and associated adverse drug events. The specific objective of this study is to determine the clinical relevance of pro-inflammatory disease-drug interactions, including establishment of the effect of pro-inflammatory diseases on drug disposition throughout disease trajectories (i.e., determining the differential effects on drug disposition based on the severity of disease). Towards this objective, this study will investigate the extent of increases in inflammation in patients with varying severities of pro-inflammatory diseases and estimate the resulting effects on drug disposition. Cytokine/chemokine concentrations and immune cell profiles will be assayed from blood samples of adult and pediatric patients with differing severities of pro-inflammatory diseases, using established disease monitoring parameters (e.g., glycosylated hemoglobin \[HbA1C\] for T2DM, C-reactive protein \[CRP\] for IBD, proteinuria for ESRD). The effect of changes in inflammation during differing severities of these pro-inflammatory diseases on drug disposition will then be estimated using established pharmacokinetic modeling approaches (e.g., physiologically-based pharmacokinetic modeling \[PBPK\]).
Study Type
OBSERVATIONAL
Enrollment
150
This observational study will not involve any interventions. Instead, the study will collect blood samples at one or multiple time points.
Indiana University Hospital
Indianapolis, Indiana, United States
RECRUITINGQuantification of Plasma Cytokine Concentrations
The first primary objective will involve quantification of plasma cytokine concentrations from patient blood samples.
Time frame: Through study completion, up to 2 years post enrollment
Phenotyping of Patient Immune Cells
The second primary objective will involve phenotyping of patient immune cells from patient blood samples.
Time frame: Through study completion, up to 2 years post enrollment
Quantification of the Plasma Concentrations of Endogenous Biomarkers of Drug Metabolism and Transport
The third primary objective will involve quantification of the plasma concentrations of endogenous biomarkers of drug metabolism and transport from patient blood samples
Time frame: Through study completion, up to 2 years post enrollment
Measures of Inflammatory Disease Severity
The fourth primary objective will involve collecting measures of inflammatory disease severity based on information collected from patients' electronic health records.
Time frame: Through study completion, up to 2 years post enrollment
Development of Adverse Events Attributable to CYP/Transporter Substrate Medications
The fifth primary objective will involve collecting the development of adverse drug events attributable to CYP/transporter substrate medications based on information collected from patients' electronic health records.
Time frame: Through study completion, up to 2 years post enrollment
Patient Genomic Markers
The secondary objective will involve determining patient genomic markers (using whole genome sequencing).
Time frame: Through study completion, up to 2 years post enrollment
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