Pharmacokinetics Lecture notes Four basic pharmacokinetic processes are Drug movement throughout the body Absorption movement

t of drug from its site of administration into blood Dissolve must dissolve before being absorbed Surface area the larger the faster Blood flow most rapid where blood flow is high Lipid solubility - the higher the faster pH partitioning Absorption - Routes IV no barriers to absorption Intramuscular good for poorly soluble drugs, "time released" Subcutaneous again no significant barriers Oral must pass through cells of epithelium, enteric coating Safer but highly variable absorption enteric, sustained-release, tablets Factors Affecting Drug Absorption Rate of dissolution Surface area Blood flow Lipid solubility pH partitioning Distribution Blood flow to tissues Exiting the vascular system once it has been delivered pass through pores in capillary wall Protein - binding Drugs can bind with proteins Parts of drugs will be bound during any given time period Impedes drugs ability to reach sites of action, metabolism, or excretion Drug Distribution Factors influencing distribution are Blood flow to tissue Exiting the vascular system The blood-brain barrier Placental drug transfer Metabolism LIVER Enzymatic alteration of drug structure Consequences of metabolism Accelerated renal excretion kidney cannot excrete highly lipid soluable

Drug inactivation Increased therapeutic action Activation of prodrugs Increased or decreased toxicity

Drug Metabolism Biotransformation Liverprimary site of drug metabolism P450 system (cytochrome P450) Drug MetabolismImplications Therapeutic consequences are Accelerated drug excretion Drug inactivation Increased therapeutic action Activation of prodrugs Toxicity variations Routes of Administration Two major groups Enteral Via gastrointestinal tract Parenteral Outside the gastrointestinal tract Usually referred to as "by injection" Common routesintravenous, subcutaneous, intramuscular Special Considerations in Drug Metabolism Age Induction of drug-metabolizing enzymes First-pass effect Nutritional status Competition between drugs Drug Excretion Removal of drug from the body Kidneyvia three processes Glomerular filtration Passive tubular reabsorption Active tubular secretion Time Course of Drug Responses Plasma drug levels Minimum effective concentration (MEC)

Toxic concentration Therapeutic range Drug half-life Loading dose Maintenance dose

Achieving and Maintaining Therapeutic Concentrations Repeated dose scheduling Drug accumulates in blood stream Plateau reached Amount administered = amount excreted

Differentiate between Loading Dose and Maintenance Dose

Loading Dose Higher amount of given drug Maintenance Dose Doses administered at intermittent (scheduled) times Drug Half-life The time for the amount of drug in the body to decrease by 50%

Excretion KIDNEY Glomerular filtration blood to tubular urine Tubular reabsorption Active tubular secretion pumps for organic acids and organic bases to urine

Monitoring drug levels Plasma drug levels Therapeutic range

Drug Half-life Time requires for the amount of drug in the body to decrease by 50% Will determine dosing requirements

Goal - plateau

Dosing Loading doses when plateau must be achieved quickly Routine smaller doses maintenance doses Peak and trough levels Maximal efficacy largest effect a drug can produce Potency one that produces its effects at lower dosages

Receptors Drugs bind to receptors to produce effects Reversible All that drugs can do is mimic the physiological activity of the bodys own molecules Block the physiological activity of the bodys own molecules

Agonists Mimic the bodys own regulatory molecules

Antagonists Drugs that block the actions of endogenous regulators

Partial agonists Mimic the actions but with reduced intensity

Drug Interactions Can have varying effects Direct chemical or physical IV preparation Drug Food Interactions Frequently decreased rate of absorption Grapefruit juice can inhibit metabolism "with food" with or shortly after meal "empty stomach" one hour prior to meal or two hours after