Pharmacokinetics I & II Flashcards
Pharmacokinetics is
What the body does to a drug
What four pharmacokinetic properties determine the speed of onset of a drug?
Absorption - drug absorption from the site of administration
Distribution - drug leave blood stream and enter ECF and ICF
Metabolism - biotransformation by liver or other tissues
Elimination - by urine, bile or feces
Effective dose (ED) is
quantity of a drug that will produce the pharmacological effects
Lethal dose is
quantity of an agent that will or may be sufficient to cause death in at least 1% of the animals or subjects given the drug
Fatal dose is
the dose that kills the 100% subject in whom it is given
Median effective dose (ED50) is
a dose that produces the desired effect in 50 per cent of a population
Median lethal dose (LD50) is
the quantity of an agent that will kill 50 per cent of the test subjects
Median toxic dose (TD50) is
dose that produces a toxic effect in 50 per cent of the population
what is therapeutic index
ratio of median lethal/toxic dose of a drug for 50% of the population (TD-50) divided by the effective dose for 50% of the population (ED50)
TI = TD 50/ ED 50 »_space;> 1 (indicates the drug is safe)
The greater the index, the wider the safety margin for the drug
Drug with different therapeutic index
High therapeutic index
- Benzodiazepines
- Certain antibiotics
- Paracetamol
Low therapeutic index
- Digoxin
- Theophylline
- Gentamicin
- Lithium carbonate
Half-life is
time taken for its plasma concentration to be reduced to half of its original value
(t½ = 0.693 × Vd /CL)
Clearance is
the rate at which a drug is removed from plasma(mg/min) divided by the concentration of that drug in the plasma (mg/mL)
Clearance = elimination rate (mg/min) / plasma drug concentration (mg/mL)
If drug follows the first-order kinetics, clearance and half-life of the drug are
constant
Loading dose is
a single or few quickly repeated doses given in the beginning of treatment to attain the great target concentration rapidly
loading dose = Cp (target) x Vd (times body weight)
Steady-state (SS) is
rate of drug administration equals the rate of elimination and plasma concentration
- Rate in = rate out = plasma concentration
- reached in 4-5 half-lives (linear kinetics)
Maintenance Dose (MD) is
repeated doses given at specific intervals after the attainment of target Css (concentration at steady state)
Maintenance dose = CL x CpSS
Calculation for dose based on age
- Young’s rule
- Cowling’s rule
- Fried’s rule (infants)
Young’s rule formula
dose of a child = age/ (age + 12) x adult dose
Cowling’s rule formula
age at next birthday (years) x adult dose / 24
Fried’s rule (infants) formula
dose for infant = age (months) x adult dose / 150
Dose based on weight (most commonly used)
-Clark’s rule (child)
Clark’s rule formula
Dose for child = Weight (Ib) x Adult Dose / 150 (average weight of adult in Ib)
Oral availability (F) is
the fraction of drug that reaches the systemic circulation after oral ingestion versus IV administration
F = AUC (oral) / AUC (iv)
Oral availability determined by
absorption and first pass metabolism
Absorption refers to
the ability of a drug to cross the gut wall into the portal vein
First-pass metabolism describes
presystemic drug elimination and can occur in the gut wall, portal vein or liver. The liver is usually the most important contributor
High first pass metabolism, ____ oral availability
low
The total amount of drug in the systemic circulation is defined by
area under the concentration-time curve (AUC)
When a medication is administered intravenously, its bioavailability is
100%
Oral bioavailability cannot be 100% because
oral drugs have slower absorption and distribution than IV drugs and subjected to first pass hepatic metabolism
Volume of distribution (Vd) determines
the distribution of drugs between blood and rest of the body
Equation for volume of distribution
Vd = Ab / Cp
Drugs with a small Vd have a ___ plasma concentration
high.
Thus, drug with small Vd mainly stay in central compartment (bloodstream)
eg drugs: phenytoin, warfarin
Drug with large Vd (high lipid soluble) have a ___ plasma concentration
low.
Thus, drug with large Vd will travel to ECF
eg drugs: propranolol, digoxin
