Transition from Pharmacodynamics to Pharmacokinetics

Patenting

•Carried out as soon as a potentially useful drug is identified

Carried out before

•preclinical and clinical trials

•Several years of patent protection are lost due to trials

•Patent a group of compounds rather than an individual structure

•Also patent production method

Phase 1

Carried out on

•healthy volunteers

•Useful in establishing dose levels

•Useful for studying pharmacokinetics, including drug metabolism

Phase 2

•Carried out on patients

•Carried out as double-blind studies

Demonstrates whether a drug is

•therapeutically useful

•Establishes a dosing regime

Identifies side effects

Phase 3

•Carried out on a larger number of patients

Establishes

statistical proof for efficacy and safety

Phase 4

•Continued after a drug reaches the market

Studies long term effects when

•used chronically

•Identifies unusual side effects

Post-marketing surveillance (PMS) - Post-marketing surveillance can further refine, or confirm or deny, the safety of a drug after it is used in the general population by

large numbers of people who have a wide variety of medical conditions

Post-marketing surveillance uses a number of approaches to monitor the safety of licensed drugs, including spontaneous reporting

•databases, prescription event monitoring, electronic health records, patient registries and record linkage between health databases.

A dosage form is "a

physical form (the way of identifying) of the drug" and used to allow for an effective delivery the drug (the active compound) to the patient.

•Active drug component(s)

Compounds used with the

•intention to provide biological effect(s)

•Could be single or multiple compounds

•Nondrug component(s)

Compounds used with the intention to provide

(i)stability

(ii)desirable color(s)/form(s)

(iii)necessary characteristic to deliver the active compound(s)

What are factors dictating the formulation of drug dosage forms?

1.Solubility (in a single compartments and in multiple compartments)

2.Stability

3.Most effective for the drug to take an effect

4.Best acceptance

Solubility- is the property of a solid, liquid, or gaseous chemical substance called

solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent

The extent of the solubility of a substance in a specific solvent is measured as the

saturation concentration where adding more solute does not increase the concentration of the solution.

How is solubility expressed?

•Grams of solute per litre of solution (g/L)

•Moles of solute per litre of solution (Molarity)

How to improve the formulation of biological compounds that are not dissolved very well in water or in biologically compatible solvents? Common approaches include:

•To create (form) salt

•To reduce particle sizes

•To find & use a better solvent

•the way that a drug is introduced into the body"

•What are common routes of drug administration?

•Oral ingestion

•Injection

•Intravenous

•Subcutaneous

•Intramuscular

Factors to consider when choosing

a route of administration

•Molecular properties of the drug

•Physiological nature of the route

•Onset of action

•The condition being treated

•Systemic or local effect (side effects)

•Metabolism

lPatient compliance

Patient compliance - Patient can easily and successfully adhere to or follow

the given instruction

How do you ensure patient compliance?

A comprehensive strategy is the key to adherence, researchers say:

•Educational:

•Behavioral:

•Affective:

Educational: Information conveyed

•verbally and in writing;

•Printout from the hospital and/or pharmacy

Behavioral:

•Telephone reminders, patient contracts, skill building, drug packaging;

Affective:

: Counseling, home visits, family support

Enteral administration

•Absorption from GI tract

•Oral ingestion

Parenteral administration

•Intravenous (IV)

•Intramuscular

subcutaneous

Other administration routes

•Sublingual

•Transdermal

•Rectal

•Pulmonary

•Topical

Enteral (oral) administration

Dosage forms:

capsule, tablet, solution, elixir, syrup

Enteral (oral): Advantage:

•The safest, most convenient, and most economical

Oral: Disadvantage

•Limited absorption (when drug is insoluble in water)

•Emesis (irritation due to the drug)

•Destruction of the drug (low pH, in the presence of food or other drugs)

Parenteral (injection) administration: Dosage forms:

injectable solution

Parenteral (injection) administration: Advantage:

•The drug is delivered in its active form

•Rapid and extensive and predictable

•The effective dose can be delivery more effectively in emergency cases

Parenteral (injection) administration: disadvantage:

•Asepsis must be maintained

•Pain

•Need some training

•Sublingual via 'under the tongue'

•Dosage form: tablets (orally disintegrating or orodispersible tablets)

Suitable drug properties:

•lipid soluble (measured by P value)

•Transdermal via though intact skin

Dosage form:

cream, paste, controlled- release topical patches

•Rectal via rectum

•Dosage form: Suppository

For

small children, unconscious, vomiting patients

•Pulmonary via lung

Dosage form:

•aerosol, volatile liquids, gases

•Topical via conjunctiva, nasopharynx, oropharynx, vagina, urethra, urinary bladder, ear, nose, anal canal for local effects

Dosage form:

Ointment, cream, drops, jelly, powder, tablet, suppository, pessary