Pharmacokinetics (PK) ®The study of the disposition of a drug ®The disposition of a drug includes the processes of ADME -  Absorption  Distribution  Metabolism  Excretion Elimination

ADME

Importance ­Without the knowledge gained from PK studies, patients may suffer: §Toxic drugs may accumulate §Useful 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 OralInjectionRectalRespiratoryTopical

Absorption  The passage of drug from the site of administration into the general circulation.  Exception: Intravenous injections I.V DrugOral Drug ImmediatelyDelayed completelyincomplete

zAbsorption 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

zMost 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 zThe movement of drug from the blood to and from the tissues

Plasma Protein Binding zMany drugs bind to plasma proteins in the blood steam zPlasma protein binding limits distribution. zA drug that binds plasma protein diffuses less efficiently, than a drug that doesn’t.

Elimination zThe irreversible removal of the parent drugs from the body Elimination Drug Metabolism (Biotransformation) Excretion

Drug Metabolism zThe chemical modification of drugs with the overall goal of getting rid of the drug zEnzymes are typically involved in metabolism Drug Metabolism More polar (water soluble) Drug Excretion

Sites of Drug Metabolism zMetabolism occurs in many tissues zE.g. brain, kidney, lung zBut mostly in the liver because … all of the blood in the body passes through the liver.

Oral Administration Intestines Liver Intravenous Administration Metabolism

Consequences Of Metabolism zDrug metabolism != Drug inactivation zThe 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 drugs  Metabolize the widest range of drugs.

Excretion zThe main process that body eliminates "unwanted" substances. zMost common route - biliary or renal zOther routes - lung (through exhalation), skin (through perspiration) etc. zLipophylic drugs may require several metabolism steps before they are excreted

ADME - Summary

Pharmacodynamics (PD) zThe study of the biochemical and physiological effects of drugs. PharmacokineticsPharmacodynamics what the body does to the drug what the drug does to the body.

Drug Interaction zWhen a drug alters the effects of another drug zDrug 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 zA First Course in Pharmacokinetics and Biopharmaceutics - available at zhttp:// zhttp://web.vet.cornell.edu/public/pharmacokinetics/pharmacokinetic s.html  The Liver and Drug Metabolism - available at zhttp:// zhttp:// zhttp:// zhttp://