Pharmacokinetics Flashcards
Pharmacokinetics
The quantitative study of drug movement in, through and out of the body
ADME
- Absorption
- Distribution
- Metabolism
- Excretion
Absorption
The process by which drugs enter systemic circulation.
The rate of absorption of a drug is determined by the properties of drugs & biological membranes of the body.
Bioavailability
Bioavailability is the fraction of administered drug that reaches the systemic circulation in an unchanged form.
Biological membranes
The outermost layer of the cell
Consisting of phospholipid bilayer along with membrane proteins & sugar molecules embedded within it.
Passive diffusion
Hydrophobic drugs move across the lipid bilayer without protein assistance
Can occur over the entire membrane
Facilitated Diffusion
SLC transporters in the membrane bind drugs and undergo conformational changes to move them across.
Uses specific protein channels
Primary active transport
ABC transporters use ATP hydrolysis to move drugs against concentration gradients
Utilizes transmembrane domains
Secondary Active Transport
SLC transporters move drugs against their concentration gradient using ion gradients
Employs specific protein channels.
Endocytosis-mediated transport
Drugs bind to membrane proteins and are internalized though vesicle formation.
Involving the entire membrane structure
Aquaglyceroporin-mediated transport
Proteins like TbAQP2 form wide conducting tunnels in the membrane for drug permeation, using specialised protein channels
Lipid bilayer interaction with hydrophobic drugs
Hydrophobic drugs partition into the inner leaflet of the membrane before being transported by proteins like P-glycoprotein.
Some factors of the drug that can affect absorption
- Lipid water solubility – lipid absorbed
- Molecular size
- Ionisation – not favoured
- Concentration – can be not favoured
- Formulation
- Bioavailability
Some factors of the body that can affect absorption
- Vascularity
- pH
- Absorptive surface area
- Mobility of GI tract
- Patient conditions
Fluid components
- Plasma
- Fats
- Interstitial fluid
- Transcellular fluid
- Intercellular fluid
Vd =
Vd = total amount of drug absorbed / plasma concentration
Distribution aims to …
Get an equal balance of substances across compartments
Lipid-water partition coefficient of a drug
Affects volume of distribution
Log P positive values indicate higher lipophilicity
Metabolism (Biotransformation)
Chemical alteration of a drug in the body to a less toxic form.
A type I metabolism reaction…
Introduces a functional group such as OH, NH2 or SH.
Usually results in an increase of hydrophilicity.
A type II metabolism reaction…
Usually results in more hydrophilic drugs.
Polar –> Phase II –> Hydrophilic
Major excretion pathways
- Renal
- Biliary
- Intestinal, salivary, sweat etc
Renal Excretion
Involves glomerular filtration, active tubular secretion, and passive reabsorption
Acidic urine increases excretion of weak bases and vice versa
Biliary excretion
Important for drugs with molecular weight > 300 g/mol
Involves active secretion into bile
Drug properties effecting secretion
- Lipophilic drugs require metabolic transformation before excretion
- Hydrophilic drugs can be directly excreted
- Protein Binding: Only unbound drugs are filtered by the glomerulus
- Active Transport: Some drugs are actively secreted in the proximal tubule
