SYSTEMIC EXPOSURE AND ASSESSMENT OF DRUG ABSORPTION 🖱
MEASURE OF DRUG ABSORPTION
WINDOW OF THERAPEUTIC CONCENTRATIONS
SAMPLING TIME
BLOOD TO PLASMA CONCENTRATION RATIO
SITE OF MEASUREMENT
non-invasive
saliva
sweat
tears
milk -lactating women
urine - major route of drug elimination
feces
invasive
whole blood
serum
plasma
cerebrospinal fluid
whole blood taken + anticoagulant + centrifuge
top - plasma
bottom - packed cells
white blood cell
red blood cell
heparin
citric acid
whole blood clot - liquid drawn out
more common because faster
no anticoagulant needed
exception - cannot used when drugs bind to clotting factor
less interference than bloood
Pharmacokinetics ANALYSIS
REASONS PERFORMED IN BLOOD
more direct measure than urine
drug distributed in blood
eliminated from body by blood
reach most part of body
PK parameters are based on drug characteristics in blood
DRUG EXPOSURE TERM
peak concentration
max drug concentration in the intravascular system at a particular dose
depends on
how much is absorbed
how quickly eliminated
peak time
time at which max drug conc occurs
depends on
how quickly absorbed
how fast eliminated
can be a way of comparison
AUC
TOTAL systemic exposure to drug
function of how much drug is systemically absorbed
early exposure
AUC up to max drug conc
k
rate constant of elimination of a process
unit per time
related directly to half-life = ln(2)/k
by default, elimination rate constant
kinetic model
major measures of systemic exposure
AUC
peak concentration
peak time
terminal half-life
called
noncompartmental
nonmodeling
general
certain window of
plasma conc
give optimal therapeutic response
where is it
too low conc - subtherapeutic response
time-wise
onset time - when conc reaches lower limit for onset response
too high conc - side effect
in between - good / therapeutic concentration
duration
time when conc above the lower limit
within the window
intensity of response varies with conc in the therapeutic window /
not necessarily directional proportion
need good info on
early exposure
peak exposure
peak time
decline of the conc-time curve a
after an extravascular dose
method
rising part- 4 samples
near true peak time - 2 or 3 points
different types of ratio
Typically
bound
unbound
sometimes
whole blood / plasma ~ factor of 2
whole blood/plasma >1
binding to blood cell components
COMPONENT OF BLOOD
hematocrit
packed-cell volume
fraction of total volume after anticoagulation of whole blood
V RBC/ total V blood
~0.45
males have higher
fraction unbound
C u/C
drug unbound / drug plasma
~0 - 1
low unbound fraction = mostly bound to plasma protein
normally protein is albumin
partition coefficient
ratio of drug conc
C bc / C u
[drug] blood cell / [drug] unbound
rho ~ (0, ∞)
case
low rho - problem with drug getting into RBC
high rho - too much drug get freely into RBC
f u * rho
[drug] blood cell/ [drug] plasma
case
low - more drug in plasma
high - more drug in blood cell
some picture lol