Pharmacokinetics Flashcards
Pharmacokinetics definition
What the body does to the drug
Pharmacodynamics definition
What the drug does to the body
PK/PD
The relationship between pharmacokinetics and pharmacodynamics
What is ADME
Absorption
Distribution
Metabolism
Excretion
Measures of ADME
A - Permeability - ability to cross membranes
D - Volume of distribution - ability to distribute from the plasma into tissue
ME - Clearance - efficiency of irreversible elimination from the plasma
What are the 2 primary measures of ADME?
-Clearance
-Volume of distribution
What are the 2 secondary measures of ADME?
AME - Bioavailability - Fraction of unchanged drug reaching the systemic circulation
DME - Half life - Time taken for plasma drug levels to decline by 50%
What parameter determines the maintenance dose rate?
Clearance is the only parameter which determines maintenance dose rate required to achieve a target plasma concentration
What if 2 drugs have the same clearance, but different volumes of distribution?
-Volume of distribution is an essential determinant of drug half-life
-2 drugs with the same clearance, but different Vd
-Bigger volume will have longer half life because drug is more distributed in tissues
What is bioavailability for IV and oral route?
IV = 100%
Oral dosing: Bioavailability depends on absorption and clearance
Graph of IV drug administration
Graph of oral administration
Differences in parameters between oral and IV dosing
-Volume of distribution cannot be calculated from oral dosing
-Oral dosing increases Tmax - time taken to reach Cmax
Definition of absorption
The process by which a drug moves from the site of administration to the site of action
What is absorption quantified by?
-Absorption rate constant (first order process)
What properties must drugs have for oral absorption?
-Water soluble in gut
-Lipophilic for membrane permeation
-Water soluble in plasma
-Absorption can be solubility and pH dependent
-Solubility is also pH dependent
What is the Volume of distribution?
-“Ration between the amount of drug in the body and the amount in the plasma”
-Total amount of drug dosed/Plasma concentration at t0
-If Vd is greater than volume that you’ve got, the drug must have gone elsewhere out of the plasma
2 ways to calculate Vd
Vd = Total IV dose/Plasma concentration at t0
Vd = Clearance/elimination rate constant (k)
Metabolism definition
-Irreversible chemical alteration of a drug by a biological
Metabolism phase 1 reaction
Introduces a new chemical group via:
-Oxidation reactions
-Reduction reactions
-Hydrolysis reactions
Aim: To produce inactive metabolites
Metabolism phase 2 reaction (prodrug)
Conjugates the molecule with charged chemical species via:
-Glucouronidation
-Acylation
-Sulfation
Aim: To decrease lipophilicity and increase solubility for enhanced excretion
Excretion definition
-Irreversible elimination of a drug from the systemic circulation
-Clearance can be used to define excretion
2 major routes of drug excretion
Renal excretion - Into the urine
-Glomerular filtration of unbound drug
-Active secretion in the kidney
-Active and passive reabsorption in the kidney
Hepatic excretion - Into the bile (faeces)
-Trans-hepatocyte
-Hepatic drug transports
-Sum of influx and efflux pumps
Other excretion routes
-Sweat
-Milk
-Saliva
