Pharmacokinetics (PK)

The study of the disposition of a drugThe disposition of a drug includes the

processes of ADME - AbsorptionDistributionMetabolismExcretion Elimination

ADME

Importance

Without the knowledge gained from PK studies, patients may suffer:Toxic drugs may accumulateUseful drugs may have no benefit

because doses are too small to establish therapy

A drug can be rapidly metabolized.

Routes Of Administration

Routes Of Drug Administration

EnteralParenteral

OralInjection RectalRespiratoryTopical

Absorption

The passage of drug from the site of administration into the general circulation.

Exception: Intravenous injectionsI.V Drug Oral Drug

Immediately Delayed

completely incomplete

Absorption relies on Passage through membranes to reach

the blood passive diffusion of lipid soluble species.

The Process

Absorption & Ionization

Non-ionised drug

More lipid soluble drug

Diffuse across cell membranes more

easily

Most drugs are absorbed in the small intestine, because It is the portal for absorption of

nutrients into blood It is surrounded by a very thin

membrane with a large surface area

Site Of Absorption

Rate & Extent

Rate - How rapidly does the drug get from its site of administration, to the general circulation?

Extent - How much of the administered dose enters the general circulation

Distribution

The movement of drug from the blood to and from the tissues

Plasma Protein Binding

Many drugs bind to plasma proteins in the blood steam

Plasma protein binding limits distribution.A drug that binds plasma protein diffuses

less efficiently, than a drug that doesn’t.

Elimination

The irreversible removal of the parent drugs from the body

Elimination

Drug Metabolism (Biotransformation)

Excretion

Drug Metabolism

The chemical modification of drugs with the overall goal of getting rid of the drug

Enzymes are typically involved in metabolism

DrugMetabolism More polar

(water soluble)Drug

Excretion

Sites of Drug Metabolism

Metabolism occurs in many tissuesE.g. brain, kidney, lungBut mostly in the liver because …

all of the blood in the body passes through the liver.

Oral Administration

Intestines

Liver

IntravenousAdministration

Metabolism

Consequences Of Metabolism

Drug metabolism != Drug inactivationThe metabolite may have

Equal activity to the drug No or reduced activity Increased activity (Prodrugs) Toxic properties, not seen with the parent

drug

The Most Important Enzymes

Microsomal cytochrome P450 monooxygenase family of enzymes, which oxidize drugs

Act on structurally unrelated drugsMetabolize the widest range of drugs.

Excretion

The main process that body eliminates "unwanted" substances.

Most common route - biliary or renal Other routes - lung (through

exhalation), skin (through perspiration) etc.

Lipophylic drugs may require several metabolism steps before they are excreted

ADME - Summary

Pharmacodynamics (PD)

The study of the biochemical and physiological effects of drugs.

Pharmacokinetics

Pharmacodynamics

what the body does to the drug

what the drug does to the body.

Drug Interaction

When a drug alters the effects of another drug

Drug A may alter these factors of drug B: Efficiency Rate of effect Side effects.

Drug Interaction

Pharmacokinetic:

Amount of drug in blood is altered

Pharmacodynamic:

The drug effect is altered

References

A First Course in Pharmacokinetics and Biopharmaceutics - available at http://www.boomer.org/c/p1/

http://www.le.ac.uk/pa/msc/pklecture.pdf http://web.vet.cornell.edu/public/pharmacokinetics/

pharmacokinetics.html The Liver and Drug Metabolism - available at

http://adultpain.nursing.uiowa.edu/MedGen/Liver.htm http://www.ttuhsc.edu/pharm/Freeman/med/DrugElim1.ppt http://www.bps.ac.uk/epharnet/adme.ppt http://www.usask.ca/medicine/pharmacology/

Mon11SEP.pdf http://www.usask.ca/medicine/pharmacology/Fri08SEP.pdf