III. Drug Metabolism  The aim of drug metabolism is to convert lipid soluble (non polar) drugs to polar metabolites easily excreted in urine.  The liver is the principle organ of drug metabolism.

The drug metabolite may be: The drug metabolite may be: Inactive: Inactive: metabolism results in termination of drug action e.g. most drugs. Active like the parent drug: Active like the parent drug: e.g. diazepam (sedative and hypnotic). Active and the parent drug is inactive: Active and the parent drug is inactive: (prodrug) e.g. methotrexate

IV. Drug Excretion  Kidney is the major rout of excretion of drugs or their metabolites.  Other channels of excretion include the lungs, intestine, skin and milk.  Drugs are eliminated from the body either unchanged as the parent drug or as metabolites (a changed form of the drug).

 Since drugs are small particles dissolved in the blood, they are usually filtered into the kidneys and then reabsorbed back into the bloodstream.  In order for the kidney to eliminate drugs from the body, the drug must somehow be prevented from being reabsorbed from the urine into the bloodstream.  The drug must be chemically changed into a compound that is less fat-soluble and therefore less capable of being reabsorbed.

Drug Product (Delivery system): Drug Product (Delivery system): The dosage form that contains the therapeutically active agent (s), generally but not necessarily in association with inactive ingredients (e.g. tablet, capsule, suspension, ….. ). Drug product selection: The process of selecting dosage form in which the drug product will be manufactured. The duration of drug therapy: The time necessary for the treatment of a disease with a drug.

Dosage regimen:  Is the manner in which a drug is taken.  It comprises calculation of the required dose (size of the dose) and adjusting dosing interval (dosing frequency) for patients. Therapeutic Objective:  It may be either the treatment, mitigation or the prevention of the disease.  It is evident that both the duration of drug therapy and the dosage regimen depend on the therapeutic objective.

Minimum Effective Concentration (MEC):  Many drugs have no demonstrable therapeutic effect or do not produce a desired degree of pharmacologic response unless a minimum concentration is reached at the receptors (sites of action).  The MEC represents the minimum concentration of a drug needed at the sites of action (receptors) to produce the desired pharmacologic effect.

Minimum Toxic Concentration (MTC): It reflects the drug concentration at which a toxic effect will appear. conc. Toxic MTC Therapeutic MEC Ineffective time

Therapeutic concentration range (Therapeutic window):  It is the range of drug concentration between the MEC and the MTC.  In other words, it is a region associated with therapeutic effect.  An optimal dosage regimen might be defined as one that maintains the plasma concentration of a drug within its therapeutic window.

Drug with narrow therapeutic window:  These drugs require conc. Therapeutic drug Toxic concentration monitoring.  Examples: Therapeutic Window e.g.1 Digoxin e.g.2 Warferin Ineffective e.g.3 Theophylline time

Therapeutic effectiveness:  Is the difference between effective therapy and toxic effects.

Biopharmaceutics:  Is the study of the effect of various pharmaceutical formulation variables on the delivery of the drug to the body under normal and pathologic conditions (impaired physiological function).Bioavailability:  Is the rate (amount/time) and extent (total amount) to which the active drug ingredient or therapeutic moiety is absorbed from a drug product and becomes available at the receptor (site of action).

 When a medication is administered intravenously, its bioavailability is 100%.  However when a medication is administered via other routes (orally), its bioavailability generally decreases (due to incomplete absorption and first- pass metabolism) or may vary from patient to patient.  Bioavailability must be considered when calculating dosages for non-intravenous routes of administration.

Pharmaceutic equivalents:  These are drug products that are identical in:  Active drug ingredient  Strength or concentration  Dosage form  Route of administration  They may differ in some characteristics e.g. colour, shape, packing, expiration time and inactive ingredients.

Bioequivalent drug products:  These are pharmaceutical equivalents whose rate and extent of absorption are not different (i.e. have similar bioavailability).  When given in the same concentration (molar dose) under similar experimental conditions).

Pharmaceutic alternatives:  These are drug products that contain the same therapeutic moiety but not necessarily as the same chemical structure. e.g.1 Betamethasone Acetate and Betamethasone Valerate e.g.2 Tetracyclin Hydrochloride and Tetracyclin Phosphate

 Also, different dosage forms containing the same active ingredients and produced by a single manufacturer are pharmaceutic alternatives. e.g.1 Sustained-release dosage form (Olfen SR) R versus a standard immediate-release drug product of the same ingredient (Olfen) R. e.g.2 Diclofenac Sodium (Declophen) R ampoule and Diclofenac Sodium (Declophen) R tablet.