Pharmacokinetics and BioPharmaceutics

Pharmacokinetics and BioPharmaceutics

• Pharmacokinetics: what the body does to the drug
• BioPharmaceutics: study of how physicochemical properties of drugs, dosage forms, and routes of administration affect the rate and extent of drug absorption

Routes of Administration

• Determined by properties of the drugs (water or lipid solubility) and therapeutic objectives (e.g. need for rapid therapeutic action)
• Enteral Route (administering the drug through the mouth)
  • Most common, convenient, and economical method of drug administration
  • Oral drugs are easily self-administered, and toxicities and/or overdose of oral drugs may be overcome with antidotes, such as activated charcoal
  • Low pH easily inactivates some drugs
  • Gives rise to the formation of EC and ER formulations
• Parenteral Route (introduces drug directly to the systemic circulation)
  • Used for drugs that are poorly absorbed from the GI tract or unstable in the GI tract
  • Used by patients unable to swallow
  • Irreversible
  • 4 major parenteral routes: Intravascular (Intravenous, Intra arterial), Intramuscular, Subcutaneous, Intradermal

Enteral Route Formulations

• Enteric Coated (EC) Formulation
  • Protects drug from stomach acid, delivering it to the less acidic intestine where the coating dissolves and releases the drug
  • Examples: Omeprazole (acid-labile drug), Aspirin (GI irritant)
• Extended Release (ER) Formulation
  • Medications have special coatings or ingredients that control drug release, allowing for slower absorption and prolonged duration of action
  • Examples: Morphine sulfate tablet

Parenteral Route Formulations

• Intravenous (IV)
  • Most common parenteral route
  • Permits rapid effect and maximum degree of control over the amount of drug delivered
  • Bolus: full amount of drug is delivered to the systemic circulation almost immediately
  • Infusion: the drug is infused over a longer period, resulting in lower peak plasma concentrations and an increased duration of circulating drug
• Intramuscular (IM)
  • Drugs can be in aqueous solutions, which are absorbed rapidly, or in specialized depot preparations, which are absorbed slowly
  • Depot preparations often consist of a suspension of drug in a nonaqueous vehicle, which diffuses out of the muscle, and the drug then dissolves slowly, providing a sustained dose over an extended interval
• Subcutaneous (SC)
  • Provides absorption via simple diffusion and is slower than the IV route
  • Minimizes the risks of hemolysis or thrombosis associated with IV injection and may provide constant, slow, and sustained effects
  • Should not be used with drugs that cause tissue irritation, as severe pain and necrosis may occur
• Intradermal (ID)
  • Involves injection into the dermis, the more vascular layer of skin under the epidermis
  • Used for agents for diagnostic determination and desensitization

Other Routes

• Oral Inhalation and Nasal Preparation
  • Provides rapid delivery of drug across the large surface area of mucous membranes of the respiratory tract and pulmonary epithelium
  • Drug effects are almost as rapid as those with IV bolus
  • Effective and convenient for patients with respiratory disorders such as asthma or chronic obstructive pulmonary disease
• Intrathecal/Intraventricular
  • Introduces drugs directly into the cerebrospinal fluid
  • Necessary for local, rapid effects in the CNS
• Topical
  • Local effect of the drug is desired
• Transdermal
  • Patch
• Rectal
  • 50% of the drainage of the rectal region bypasses the portal circulation, minimizing the biotransformation of drugs by the liver
  • Useful if the drug induces vomiting, or if the patient is unconscious

Mechanisms of Drug Absorption

• General Principle:
  • A cell membrane is a semi-permeable structure composed primarily of lipids and proteins
  • Drugs must be in aqueous form and non-ionized
  • The fluid mosaic model explains the transcellular diffusion of polar molecules
  • Drugs may be transported by several mechanisms
  • Drugs bound to proteins and macromolecules do not easily cross cell membranes
  • Non-polar lipid-soluble drugs traverse cell membranes more easily than do ionic or polar water-soluble drugs
  • Low molecular weight drugs diffuse across a cell membrane more easily than do high molecular weight drugs

Transport Systems

• Passive Diffusion
  • Dominant transport mechanism but the slowest
  • None energy requiring
  • Fick's Law: dQ = DAK (CGI – Cp) / dT * h
  • Factors that affect passive transport: surface area, concentration gradient, thickness of membrane, diffusion coefficient
• Facilitated Diffusion
  • Other agents can enter the cell through specialized transmembrane carrier proteins that facilitate the passage of large molecules
  • Does not require energy, can be saturated, and may be inhibited by compounds that compete for the carrier
• Active Transport
  • Energy-dependent, driven by the hydrolysis of ATP
  • Capable of moving drugs against a concentration gradient
  • Saturable
  • Selective and may be competitively inhibited by other cotransported substances
• Endocytosis and Exocytosis
  • For large size molecules
  • Endocytosis: involves engulfment of a drug by the cell membrane and transport into the cell by pinching off the drug-filled vesicle
  • Exocytosis: more on secretion of substances out of the cell through similar process of vesicle formation

This quiz covers the concepts of pharmacokinetics and biopharmaceutics, including how the body affects drugs and how physicochemical properties of drugs affect biological action.