Pharmacokinetics

Pharmacokinetics is the discipline that describes the concentration to a drug over time in the body, most commonly the blood plasma compartment.

Pharmacokinetics
These are major organs in which transporters are involved in drug absorption, distribution and elimination.

http://rjcoms.com/drug_discovery/310371/predicting_transportermediated _drugdrug_interactions_based_on_in_vitro_cell_permeability_assays.html

Main reasons for attrition in drug development

Nature Reviews Drug Discovery 2, 192-204 (2003)

Bioavailability and ADME Prediction

Absorption Distribution Metabolism Elimination

Pharmacokinetic Bioavailability

C.A. Lipinski et al. Adv. Drug. Delivery Reviews 23 (1997) 3.

Representation of the pharmacokinetics process and different models in use to study the pharmaceutical profile

http://biocomp.health.unm.edu/biomed505/Course/Cheminformatics/advanced/properties/ADME_tox.htm

Distribution
Most important organ: The brain

Drugs acting on the central nervous system (CNS) must cross the blood-brain barrier (BBB) Peripheral drugs may be required not to pass the BBB to avoid CNS side effects

Virtual Screening
106 small-molecule compounds vHTS: MM + scoring functions N x 102 leads Filters: ADMET / QSAR M x 101 leads

Filters: synthesis / manufacturing / IP / patent / biological assays

1 - 5 leads

In silico ADME Filter

3D-Pharma
Binary Fingerprints

Integration of Chemoinformatics and Bioinformatics

Genomic Biology Large Molecule Targets Small Molecules Computational chemistry

Assays

Bioinformatics

High Throughput Screening

Cheminformatics

In silico

Pharmacokinetics

http://www.rmi-pharmacokinetics.com/Pharmacokinetics.asp

Pharmacokinetics - BBB

http://www.pharmainfo.net/reviews/overview-brain-targeting-drug-delivery-system

Pharmacokinetics

Pharmacokinetics

http://www.pharmacology2000.com/General/Pharmacokinetics/kinobj1.htm

http://www.cbligand.org/BBB/

In Silico Screening

Bioavailability & ADME Prediction

Absorption Distribution Metabolism Elimination

Pharmacokinetic Bioavailability