Schematic illustration of the interaction between CYP2C8 and its glucuronide substrates. Schematic illustration of the interaction between CYP2C8 and its.

Slides:



Advertisements
Similar presentations
CYP2C8 and Drug Interactions
Advertisements

Representative 10-s EEG recordings from GAERS: during baseline (prior to injection of any drug) (i), following the i.c.v. injection of 4 μl of vehicle.
Location of CYPs in the cell
Overview of the MHC I antigen-processing pathway TAP, transporter associated with antigen processing; ER, endoplasmic reticulum; MHC I, major histocompatability.
Schematics of GABAA receptor structure and function.
Parallels in antimicrobial peptide mechanisms of action and resistance
Diversity of Polyubiquitin Chains
Requirement for a β subunit for the modulation of whole-cell CaV2
Figure 4 Activation of clopidogrel via cytochrome P450
COX-1 and known variants.
Comparison of the model incorporating daily dose to that incorporating Cmax. Comparison of the model incorporating daily dose to that incorporating Cmax.
Evaluation of models incorporating the base covariates.
Phosphorylation and sequence disorder in microtubule-associated protein Tau.A, schematic illustration of the domain profile of Tau with all known phosphorylation.
The context-sensitive half-times for commonly used intravenous anesthetic drugs. [Reproduced from Reves JG, Glass PSA, Lubarsky DA, McEvoy MD, and Martinez-Ruiz.
Formation and metabolism of DOPAL and DOPEGAL
Schematic summary of innate signaling pathway components and filaments
Representative radio-HPLC chromatograms for individual pooled methanolic fecal extracts for periods of maximum recovery of radioactivity after dosing of.
HPLC tracings of resveratrol (RV) and its major sulfate conjugates M4/M5 in the plasma from three subjects. HPLC tracings of resveratrol (RV) and its major.
Retroviral vector propagation in helper cells and structure of a prototypical vector. Retroviral vector propagation in helper cells and structure of a.
Mean (± S.E.) change from baseline in the 6-min walk distance for bosentan (n = 21) and placebo (n = 11) groups. Mean (± S.E.) change from baseline in.
Total ion current-EMS chromatograms of SB939 and its metabolites after incubation in liver microsomal fractions for 60 min at a concentration of 50 μM.
Structure of solid lipid nanoparticles (SLNs).
Phylogenetic tree of the human class Frizzled receptors FZD1–10 and SMO created with the ClustalW2 software (ver ;
Alterations in PUFA metabolism and flux through the P450/sEH pathway related to hypoxia and activation of the renin-angiotensin system. Alterations in.
The three primary ADC components that determine which cells are targeted (antibody), how the drug is released (linker/trigger), and the mechanism of action.
T-type calcium channel regulators.
Microglia and the Immune Pathology of Alzheimer Disease
Mechanisms of H2S release from S-aroylthiooximes (SATOs).
Model B. The melatonin-produced increase in extracellular dopamine concentration in the striatum is prevented by the CYP2D inhibitor propafenone in pargyline-pretreated.
Cytotoxic activities of polymer micelles containing CFZ in H460 (A) and select micelle formulations in RPMI-8226 (B) cell lines. Cytotoxic activities of.
Cytotoxic effects of PM1 and PM2 empty particle controls and coincubation of CFZ with empty particles tested in H460 (A) and RPMI-8226 (B) cells. Cytotoxic.
Calcium channel structure and ligand binding sites.
Geometric mean concentration-time profiles of (A) racemic BUP, R-BUP, and S-BUP; (B) racemic OHBUP, RR-OHBUP, and SS-OHBUP; (C) racemic ERY, SR-ERYHBUP,
The additive model assumes unspecific effects of equal size in both the placebo and drug arm or groups of studies or experiments. The additive model assumes.
Interaction of drug substrates and the AcrB-binding protomer analyzed with Autodock Vina docking software. Interaction of drug substrates and the AcrB-binding.
Figure 4 Intracellular distribution and
RLR domains and signaling.
Comparison of the observed and calculated CLR values of taurine and GCDCA-S. Comparison of the observed and calculated CLR values of taurine and GCDCA-S.
(A) Illustration depicting two types of pharmacokinetic instability of an ADC. Conjugating an antibody with drug can accelerate its clearance (green versus.
Three drug delivery strategies for crossing the blood-brain barrier.
Effects of gemfibrozil on the exposure (area under the plasma drug concentration-time curve) to different CYP2C8 substrate drugs. Effects of gemfibrozil.
Results of thermogravimetric measurements of peptide ghrelin antagonist (GhA) and loaded into PSi microparticles. Results of thermogravimetric measurements.
Schematic illustration of exposure-driven response models (upper row) and biophase-driven response (bottom row). Schematic illustration of exposure-driven.
Half-life of removal from subcutaneous administration site after subcutaneous administration of fluorescence-labeled VEGF-C156S, ovalbumin (OVA), bovine.
Fraction of dose (mean, n = 3–4) recovered in peripheral lymph following subcutaneous administration to sheep for a series of small molecular compounds.
Stereoimage of three independent docking simulations of the interaction between clopidogrel acyl 1-β-d-glucuronide and the active site of CYP2C8. Stereoimage.
Drug clearance by metabolism can also decrease with declining kidney function. Drug clearance by metabolism can also decrease with declining kidney function.
Damage-associated molecular pattern (DAMP)-induced activation of Toll-like receptors (TLRs). Damage-associated molecular pattern (DAMP)-induced activation.
CBD elevates AEA levels in poly-(I:C)–stimulated HaCaT cells after 6 hours. CBD elevates AEA levels in poly-(I:C)–stimulated HaCaT cells after 6 hours.
Schematic diagram illustrating a theoretical model of amygdala modulation of memory and synaptic plasticity in the hippocampus. Schematic diagram illustrating.
The microchip-based drug delivery device and overview of study design
CBD and other phytocannabinoids are not cytotoxic in HaCaT cells.
The CYP2C8 gene is located to the CYP2C gene cluster on chromosome 10.
Schematic illustration of MRP4 regulation pathway.
The cyctoprotective endoplasmic reticulum (ER) stress mechanism [32].
(Left) Observed (symbols) and model-predicted (lines) response (tail flick) vs. time of drug X after different doses given by the intravenous (red) and.
Unbound drug concentrations in plasma (dotted) and brain ISF (solid, calculated from recovery and dialysate concentration) following repeated subcutaneous.
AEA and URB597 reduce MCP-2, IL-6, and IL-8 levels in poly-(I:C)–stimulated HaCaT cells after 6 hours. AEA and URB597 reduce MCP-2, IL-6, and IL-8 levels.
Activation and desensitization of the α7 nAChRs.
Role of CETP in plasma cholesterol transport.
The effect of a change in the expression level of the receptor and the binding affinity on the subcutaneous bioavailability of mAbs. The effect of a change.
Schematic representations of pulmonary hypertension.
Concerted model for maltose transport.
Neighbor joining tree showing relationships between the human cannabinoid CB1 and CB2 receptors and other human rhodopsin α-group type G protein-coupled.
Signaling pathways of galanin receptors.
Average trastuzumab serum concentrations in female minipigs following single subcutaneous administration of trastuzumab in formulations without and with.
Allometric relationship between the lymph flow in the thoracic duct and species body weight. Allometric relationship between the lymph flow in the thoracic.
Topology of human Cx26 and Cx43 indicating crucial domains as well as peptides that affect protein and channel functions. Topology of human Cx26 and Cx43.
Sites for absorption, distribution, metabolism, enterohepatic recycling (EHC), and elimination of mycophenolic acid (MPA). Sites for absorption, distribution,
Toll-like receptors, adapter proteins, and signaling molecules.
Presentation transcript:

Schematic illustration of the interaction between CYP2C8 and its glucuronide substrates. Schematic illustration of the interaction between CYP2C8 and its glucuronide substrates. CYP2C8 and the UGT are localized on opposite sites of the endoplasmic membrane (A). The drug is glucuronidated by the UGT (B). Hereafter, the glucuronide crosses the endoplasmic membrane and binds into CYP2C8 (C). Then, the glucuronide is either metabolized by CYP2C8 and released as a metabolite (D, left), e.g., desloratadine glucuronide, and diclofenac acyl glucuronide, or it is metabolized to a reactive agent that inactivates CYP2C8 (D, right), as for clopidogrel acyl 1-β-d-glucuronide and gemfibrozil 1-O-β glucuronide. CYP2C8 has been suggested to exist as a dimer (Hu et al., (2010), Schoch et al., (2004)). ER, endoplasmic reticulum. Janne T. Backman et al. Pharmacol Rev 2016;68:168-241 Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics