bioavailability
fraction of drug absorbed into systemic circulation
measure of the extent of absorption of a dose
reduced by first pass metabolism (chemical breakdown of a drug that occurs prior to reaching circulation)
volume of distribution
measure of apparent space in the body available to contain the drug
clearance
measure the body’s efficiency in eliminating drug from circulation
half-life
time required to change plasma concentration by 50%
absolute bioavailability
systemic availability of a drug after extravascular administration compared to IV administration
may not exceed 100%
F of extravascular dosage form divided by F of IV dosage form
relative bioavailability
difference in systemic availability between any two formulations of the same drug
may exceed 100%
F of extravascular dosage form 1 divided by F of extravascular dosage of form 2
bioequivalence
rate and extent of bioavailability of the active ingredient in two products are not significantly different under suitable and identical test conditions
tablet and capsule formulations of the same medication
pharmaceutical equivalence
when two drug products contain the same active ingredients and are identical in strength or concentration, dosage form, and route of administration
brand and generic versions of the same medication
clinical pharmacokinetics
bioavailability
volume of distribution (Vd)
clearance
half-life
Vd single compartment model
Considers the body as a single homogenous compartment
all drug administered occurs directly into the central compartment
distribution is instantaneous throughout all volume
Vd multicompartment model
Recognizes that not all drugs will distribute homogeneously throughout the body
There is an equilibrium between the vascular and extravascular spaces
Distribution will take time
clearance represented in unit of
volume/time
first order elimination
fraction of drug removed per unit of time is constant
amount of drug removed per unit of time changes
ex. 10% of the drug removed per hour, 100mg at hour 1 = 10mg removed, 90mg at hour 2 = 9 mg removed
zero order elimination
amount of drug eliminated per unit of time is constant
fraction of drug removed per unit of time change
ex. 10mg of the drug removed per hour, 100mg at hour 1 = 10mg removed (1/10), 90mg at hour 2 = 10mg removed (1/9)
linear kinetics
will only follow first order or zero order elimination
relationship between the drug dose and drug concentration are proportional
non-linear kinetics
may switch between first order and zero order elimination
relationship between drug dose and drug concentration are not proportional
caused by saturation of transport, metabolism, elimination
steady-state concentration
drug elimination equals the rate of drug availability
achieved after 4-5 half-lives when drug is administered at a constant rate
maintenance dose
dose required to maintain steady state
(target concentration x clearance)/bioavailabiliy
loading dose
used when rapid onset of effect needed, aim of achieving target concentration rapidly
(target concentration x volume of distribution)/bioavailability
quantal dose-response curve
determines the median effective dose and median lethal dose
median effective dose (ED50)
dose at which 50% of individuals exhibit the desired therapeutic effect
different than potency described in graded dose response curves
difference between median effective dose and potency
potency describes a drug concentration and cellular activation
median effective dose describes desired response to a dose of administered medication
median lethal dose (LD50)
dose that kills approximately 50% of the animals in a test group
therapeutic index
defines how selective the drug is in producing desired effects vs serious adverse effects
calculated through the LD50/ED50
closer to 1 indicates effectiveness = lethal
