Lecture 7 Flashcards
Bioavailability
fraction of administered drug that reaches systemic circulation in a chemically unchanged form.
Factors affecting bioavailability:-
1. First pass metabolism
2. Hepatic disease
3. Enterohepatic cycling
4. Solubility of the drug
5. Chemical instability
6. Nature of the drug formulation
First pass metabolism
When drugs are administered orally, they have to pass via gut wall to portal vein to liver and then finally enters systemic circulation; during this passage certain drugs get metabolised, removing or get inactivated before they reach systemic circulation. This process is known as first pass metabolism.
Its results in:-
• decreased bioavailability of the drug and diminished therapeutic response
For example; lignocaine (liver), isoprenaline (gut wall)
To avoid first pass metabolism, some drugs are administered parenterally. I.e, lignocaine is given through I.V route
Hepatic disease
It results in decreased metabolism and increased bioavailability of the drugs that undergo first pass metabolism.
I.e; lignocaine and propranolol
Enterohepatic cycling
• it increases the bioavailability of the drug
I.e morphine
Solubility of the drug
• very hydrophilic drugs are poorly of absorbed because of their inability to cross lipid rich membranes
• Drugs which are extremely hydrophobic are also poorly absorbed because they’re insoluble in aqueous bodily fluids
• for a drug to be readily absorbed it must be largely hydrophobic but must have some solubility in aqueous solutions. Reason why many drugs are weak acids or weak bases.
Chemical instability
• Some drugs like penicillin G are unstable in PH of gastric contents
• insulin is readily destroyed in GI tract by degradative enzymes
Nature of the drug formulation
Particle size, salt form, crystal polymorphism, enteric coating and presence of excipients which can alter the rate of absorption
Bio equivalence
Two related drugs are said to be bio equivalence if they show comparable bioavailability and similar times to achieve peak concentration.
Therapeutic equivalence
Two drugs are therapeutically equivalent if they have comparable efficacy and safety.
Clinical effectiveness often depends upon;
• Maximum serum drug concentration to achieve peak concentration
• Time required (after administering) to achieve peak concentration
Plasma half life
It is the time required for the plasma concentration of the drug to decrease by 50% of its original value.
I.e; plasma t1/2 of lignocaine is 1h.
Clinical importance:
• determine the duration of drug action
• determine the frequency of drug administration
• estimate the time required to reach the study state
Factors affecting:
1. Type of kinetics ; first or zero order
2. Disease of organs of metabolism; liver disease
3. Enzyme inhibitors; deccreased metabolism
4. Enzyme inducers; increased metabolism
5. Active metabolites
6. Enterohepatic cycling
5. Diseases of organ of excretion; renal failure
Examples:-
Aspirin - 15 mins
Propranolol - 4h
Ranitidine - 2h
Digoxin - 36h
Steady state
Steady state concentration exists when
Rate of administration = rate of drug elimination
Input = output
Clearance
clearance is a pharmacokinetic measurement of the volume of plasma from which a substance is completely removed per unit time
CL= rate of drug elimination/ plasma concentration
First order kinetic
Constant fraction of the drug in the body is eliminated per unit time
I.e 100 mcg/ml 1h-t1/2 -> 50 mcg/ml 1h-t1/2 -> 25mcg/ml
• drugs following first order kinetic is always constant
• most drug’s follow first order kinetics
Zero order kinetic
A constant amount of a drug in the body is eliminated per unit time.
The rate of elimination is independent of plasma drug concentration,
e.g. ethanol is eliminated from the body at the rate of about 10 mL/h
200mcg/mL 1h-10 mcg -> 190mcg/ml 1h-10mcg -> 180 mcg/mL
• drugs that follow zero kinetic order are never zero
