1.4 Pharmacokinetics

Definition of Pharmacokinetics

What the body does to the drugs

What are the 4 key issues of pharmacokinetics?

• ADME

  • Absorption

  • Distribution

  • Metabolism

  • Excretion

What is absorption?

• Drug must move from administration site into another tissue or bloodstream

• Dependent on route of administration

What are types of administration?

• Entral

• Parentral

What is an entral administration route?

Administration of a drug through the alimentary (digestive) canal

What is a parentral administration route?

Administration of a drug through any other way other than entral

What is the golden rule of administration?

The more direct the administration of the drug is to the tissue the more beneficial the effects will be with less drugs used and less side effects

Examples of entral drug administration route

• Oral

• Buccal/cheek

• Lingual/sublingual

• Rectal

Examples of parentral administration route

• Injection

  • Intravenous, intramuscular, intra-arterial, etc.

• Inhalation

• Topical

• Transdermal

What are the trade-offs between using entral and parentral administration routes?

• Entral

  • Easier to administer

  • Less predictable administration

    • Drug has to cross many hurdles to cross

• Parentral

  • More difficult to administer

  • More predictable administration

    • Drug has less hurdles to cross

What is bioavailability?

The percentage of the drug’s dose that appears in the bloodstream

When can bioavailability be measured?

When a drug is administered through an oral or transdermal patch

Example of Bioavailability

• 100 mg of drug A is taken and only 50 mg of the dose appears in the bloodstream

• Drug is only 50% bioavailable

What is the first pass effect?

The concentration of a drug administered orally is reduced during its first pass through the liver

Where are drugs absorbed?

In the GI tract after it passes through the hepatic portal vein via the liver

How extensive can the first pass effect be?

• Some drugs will not make it past the first pass effect

• Important to know the percentage of drug that will not survive the FPE to adjust the dosage

What is distribution?

Drugs crossing the cell membranes and tissues to reach the target site

What factors affect distribution?

• Administration route

• Psychochemical drug properties

• Drug binding to plasma proteins

• Ability for drug to pass through barriers

How is distribution measured?

• Volume of distribution

• Ratio of the amount of drug distributed to drug’s concentration in the plasma

What does the volume of distribution indicate?

• Indicates if enough of the drug will reach the target site

How is volume of distribution interpreted?

• Compared to value of 42 (amount of water in the body)

  • Vd = 42, even distribution

  • Vd < 42, drug is retained in plasma

  • Vd > 42, drug is retained in tissues

What is drug storage?

Accumulation of a drug in the body when it is distributed to certain sites

What are primary drug storage sites?

• Fat

• Muscle

• Bone

• Liver

• Kidneys

• Other tissues/organs

What are issues with drug storage?

• Local tissue can be damaged

• Redistribution of drug

What is redistribution?

When a drug that has been stored in a tissue begins to leak drug back out into the system

What is metabolism?

Transformation of a drug to a less active, or inactive, byproduct or metabolite

What is biotransformation?

• Transformation of a substance that is easier for the body to eliminate

  • Chemical drug substances usually become more polar and water soluble metabolite for kidney’s to excrete

What is the primary site of metabolism?

Liver

How do enzymes metabolize drugs?

• Phase 1 rxns

• Phase 2 rxn

What are examples of phase 1 rxn?

• Oxidation

• Reduction

• Hydrolysis

What are examples of phase 2 rxns?

• Conjugation

  • Addition of a second molecule to the byproduct of a phase 1 rxn

What are active metabolites?

Metabolites that can continue to produce effects and side effects for a prolonged period

What is excretion?

Process body goes through to eliminate drugs and metabolites

What is the primary site of extretion?

Kidneys

What percentage of drug excreted remains intact when excreted?

25-30%

What is reabsorption?

Return of substance from the kidneys into the body system