Pharmacokinetics is the study of the processes that affect drug distribution and the rate of change of drug concentrations within various regions of the body. These processes are also collectively referred to as ADMET for drug adsorption, distribution, metabolism, excretion, and toxicity.

We also need to distinguish pharmacokinetics from similar terms. Therefore, pharmaceutics concerns the formulation and preparation of the drug to achieve a desired drug availability within the body, pharmacodynamics is concerned with the time course of the treatment response that results from a given drug, and the actual physiological response that results from a drug is the subject of pharmacology.

The application of pharmacokinetics to toxic/hazardous substances is called toxicokinetics.

FDA Drug Approval Process

Pharmacokinetics

Therapeutic Window

PharmacodynamicsEffect oftreatment

Graded response saturates and may be described by

CC

CEE

50

maxC is what comes from the PKanalysis hence one then knowsthe treatment response fromequation at left

Drug Entry

1. Prefer plasma drug concentration since it is quicker and not interfered by hemolysis and release of RBC proteins2. Drug concentration as measured is usually the total plasma concentration or what is known as the unbound and bound drug concentration3. Drug effect, distribution, and elimination is due to unbound drug concentration4. fu is the fraction unbound = Cu/Ctotal and is usually constant so either Cu or Ctotal can be used in a PK analysis, just be sure to know what you are using

Splanchnic circulation takes the drug from the GI tractdirectly to the liver for what is called first pass elimination,which can significantly reduce the amount of drug thatis available for a given dose.

Diffusion through the lipid bilayer depends on the solubility of the drug.

Environment is aqueous, lipid, then aqueous in the cell

Standard way of describing the lipid solubility of a drug is by the logPWhich is also the octanal/water partition coefficient which is defined as:

W

OWO C

CKP 10/10 logloglog

logP > 0 means the drug is more soluble in octanal than in water and aretherefore called lipophilic drugs

logP < 0 means the drug is less soluble in octanol than in water and aremore hydrophilic

Optimal logP for passive diffusion across the lipd bilayer of cells is around2-3

Increasing lipophilicity

Passive transport: rate = P S C

Carrier mediatedTransport: Cf

K

VKCffor

CfK

CfVrate U

ttU

Ut

U

maxmax ,

Note only the unbound drug is transported, bound drug is usuallywith albumin which is too big

Perfusion limited - Tissue membranes present no resistance to drug transport

Permeability limited – membranes of the capillaries and cells limit transport

Perfusion rate limited

Permeability-limited

Permeability ratelimited