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