lecture 1 - intro to pharmacokinetics Flashcards
What are the 4 stages of pharmacokinetics when a drug enters the body?
ADME - absorption, distribution, metabolism, excretion
What is the aim of drug dosing?
To ensure the drug plasma concentration is within the optimal therapeutic range for a sufficient duration.
What is the symbol for Drug plasma concentration?
Cₚ
What is the ‘AUC’ in drug dosing?
Area Under the Curve
What does the AUC in a drug dosing curve correspond to?
The fraction of the dose administered that reaches the systemic circulation, i.e. body exposure
What is the Cₚ AUC dependent on?
The dose administered, and the rate of drug elimination
What is the unit of AUC?
Conc. (mg) * hours / volume (L)
What are the 2 overall routes of drug administration?
Enteral, parenteral
What is enteral drug administration?
Absorption via any part of the enteric system/GI tract
What are the 3 routes of enteral drug administration?
oral, sublingual, rectal
What is parental drug administration?
non-enteral, systemic delivery
What are the methods of parenteral drug administration?
IV bolus/infusion, Injections (Intraarterial, intramuscular, subcutaneous), topical, inhalation
What is the metabolic disadvantage of oral enteral delivery?
Drug is subject to 1st pass metabolism - by the liver.
What measure is used to measure the amount of a drug that reaches the systemic circulation in its active form?
Fraction of dose (F)
What does Fraction of dose (F) measure?
Oral availability - the proportion of a dose that reaches the systemic circulation in its active form
What is the Fraction of dose (F) for an intravenously administered drug?
1 - all of the drug enters the circulation directly
What is the equation for Fraction of dose (F)?
F% = AUC(oral)/AUC(IV) *100
What is the oral availability of a drug dependent on?
drug absorption, first pass metabolism
What is drug absorption?
transport of the drug from site of absorption into the systemic circulation
What is the rate of drug absorption dependent on?
drug lipid solubility, gastric pH, pKa, surface area, blood flow, GIT transit time, presence of other drugs
What is the rate of the first pass metabolism of drugs dependent on?
gastric pH, GIT motility, metabolic enzymes in gut and liver, drug breakdown, hepatic mass & perfusion
What type of lipid membrane transport do most drugs use?
passive transport (non-energetic)
What metabolic enzyme systems are involved in the first pass metabolism of drugs?
GI lumenal enzymes, gut wall enzymes, bacterial enzymes, hepatic enzymes
What physico-chemical properties of drugs affect their absorption?
molecular weight, hydrophilicity/lypophilicity, ionisation status
What is the unit for drug clearance?
vol of plasma cleared/unit time
What are the 2 key types of drug clearance?
metabolic, renal
Where does metabolic drug clearance predominantly occur?
The liver
What is the relationship between AUC and drug clearance?
Inversely proportional - increasing clearance decreases AUC
What is the rate of drug distribution dependent on?
membrane permeability, organ perfusion
What measure is used to quantify how well a drug is distributed throughout the body?
Volume of distribution (Vd)
How is volume of distribution of a drug calculated?
amount administered/concentration in plasma
What is the purpose of calculating loading dose?
Allows a steady plasma concentration to be achieved quickly
What is the equation for calculating loading dose?
LD = volume of distribution * target plasma conc.
What is the reciprocal of pharmacokinetic half life?
The drug elimination rate constant
How is the drug elimination rate constant calculated?
k = 0.693/t1/2
How is half life calculated from volume of distribution & drug clearance?
t1/2 = (0.693 * Vd)/Cl
