(A) Illustration depicting two types of pharmacokinetic instability of an ADC. Conjugating an antibody with drug can accelerate its clearance (green versus.

Slides:

Advertisements

Similar presentations

Clinical Pharmacokinetics Fundamental hypothesis: a relationship exists between the pharmacological or toxic response to a drug and the accessible concentration.

Advertisements

A review of modifications to recombinant antibodies: attempt to increase efficacy in oncology applications Mitchell E. Reff, Cheryl Heard Critical Reviews.

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.

Copyright © American Speech-Language-Hearing Association

Antibody Drug Conjugates Services Antibody-drug conjugates Antibody-drug conjugates (ADCs) are a very important class of highly potent drugs designed as.

Dose-response relationships. A

The large hepatic portal vein that collects blood from various segments of the GI tract also perfuses the liver. Source: Drug Elimination and Hepatic Clearance,

Parallels in antimicrobial peptide mechanisms of action and resistance

بهداشت فردي.

בטיחות בתעשייה בהיבט חברות הביטוח

Scratching the Surface of Immunotherapeutic Targets in Neuroblastoma

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.

Nat. Rev. Clin. Oncol. doi: /nrclinonc

The context-sensitive half-times for commonly used intravenous anesthetic drugs. [Reproduced from Reves JG, Glass PSA, Lubarsky DA, McEvoy MD, and Martinez-Ruiz.

Figure 2 Circadian and ultradian fluctuations in corticosterone

A, reversed phase HPLC separation and profile of products from HUVEC and human PMN coincubations. A, reversed phase HPLC separation and profile of products.

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.

Mechanism of stabilization of the closed conformation of the umami receptor VFTM by IMP (green). Mechanism of stabilization of the closed conformation.

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.

Scratching the Surface of Immunotherapeutic Targets in Neuroblastoma

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.

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.

Pharmacokinetic Evaluation of the Drug Interaction between Intravenous Itraconazole and Intravenous Tacrolimus or Intravenous Cyclosporin A in Allogeneic.

Selvadurai Muralidharan, Kalaimani Jaya Raja Kumar

RLR domains and signaling.

Proteinuria and hypertensive nephrosclerosis in African Americans

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.

Volume 80, Issue 3, Pages (August 2011)

Volume 20, Issue 2, Pages (February 2013)

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.

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

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.

Dose-normalized plasma concentration-time curves of a mAb following subcutaneous (SC) and intravenous (IV) administration to cynomolgus monkeys (mean ±

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.

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.

CBD and other phytocannabinoids are not cytotoxic in HaCaT cells.

The CYP2C8 gene is located to the CYP2C gene cluster on chromosome 10.

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.

Rituximab immunotherapy: it’s getting personal

Involvement of cys298 in the interaction of PGA1 with AKR1B1.

In Memoriam: E. Donnall Thomas

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.

Neighbor joining tree showing relationships between the human cannabinoid CB1 and CB2 receptors and other human rhodopsin α-group type G protein-coupled.

Fig. 1 Study design and antibody pharmacokinetics.

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.

Plasma concentration-time profile after oral administration of a single dose. Plasma concentration-time profile after oral administration of a single dose.

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.

Presentation transcript:

(A) Illustration depicting two types of pharmacokinetic instability of an ADC. Conjugating an antibody with drug can accelerate its clearance (green versus blue line). (A) Illustration depicting two types of pharmacokinetic instability of an ADC. Conjugating an antibody with drug can accelerate its clearance (green versus blue line). Loss of drug from the ADC during circulation results in less drugged antibody relative to total antibody (blue versus black line). (B) Conceptualized relationship between drug antibody ratio (DAR), antitumor activity (efficacy), and elimination of antibody from blood (clearance). Excessive drugging can lead to a loss of efficacy due to reduced ADC exposure. Paul Polakis Pharmacol Rev 2016;68:3-19 Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics