1.2 Pharmacokinetics Flashcards
Clearance Volume of Distribution Half-Life Metabolism Protein Binding First Pass Effect Bioavailability Absorption Distribution
Pharmacokinetics
The handling of the drug by the body
ADME
Absorption
Distribution
Metabolism
Excretion
List possible routes of drug administration
Oral Rectal Percutaneous Intravenous Intramuscular Intrathecal Inhalation
Plasma Protein Binding
Drugs that bind to proteins within plasma. Albumin most common. Only free fraction of the drug is active and can be eliminated
Clearance
Irreversible elimination of the drug
Two possible forms of Clearance
Excretion of unchanged drug. (e.g. by the kidneys in the urine)
Metabolisms into a different chemical (liver)
How is Clearance quantified?
Volume of blood cleared of drug per unit time (e.g. L/h).
What effects how much a drug can be eliminated by a given organ
The blood flow though that organ.
What does clearance determine?
Maintenance dose. The dose required to maintain target plasma concentration at steady state
Volume of Distribution
Hypothetical volume of body fluid necessary if total amount of drug were distributed at same concentration as plasma; Can give approximation of distribution of compound throughout the body.
Volume of Distribution (V) = Total drug in body (mg) / Plasma [drug] (mg/L)
Why is knowing VD important?
Allows calculation of the loading dose.
Loading dose
An initial dose of a drug that is used to achieve a desired drug level. Loading dose (mg) = Volume of distribution (L) x Target [plasma] (mg/L)
Half-Life
Time taken for drug in body to be reduced by half
First Order Kinetics
Type of kinetics when a constant percentage of substrate is metabolised per unit time. Half Life will not change by variations in dose. Changes in [plasma] will change the rate at which it is cleared.
Zero Order Kinetics
Drug elimination with a constant amount metabolized regardless of drug concentration
What does Half-Life determine?
A drugs duration of action after a single dose Time to reach steady state with constant dosing Dosing frequency (how often someone needs to take a particular dose)
First Pass Effect
Extraction and metabolism of orally ingested drugs before they reach the systemic circulation.
What organs contribute to the first pass effect
Largely the Liver, sometimes the gut wall
Bioavailability
Percentage of total drug that reaches the systemic circulation.
Phase 1 Metabolism
Oxidation, Hydrolysis etc.
Phase II Metabolism
Conjugation
Saturation Pharmacokinetics
Zero-Order Kinetics. Duration of drug will depend on dose. Relationship between dose and [steady-state] is unpredictable
