Pharmacokinetics (TOLS 1 - Basics of PK)

uses of pharmacokinetics

predict drug conc

calculate dosage regimen

quantitative assessment of effect of disease on drug disposition

determine drug-drug interaction mechanism

predict drug conc vs effect relationships

Pharmacokinetics

what the BODY does to the drug

ADME

pharmacodynamics

what the DRUG does to the body

ADME

absorption, distribution, metabolism, excretion

absorption

process where drug moves from site of admin to systemic circulation

distribution

reversible transfer of drug to or from site of measurement

what can influence distribution

tissue perfusion

protein and tissue binding

permeability of tissue to drug

metabolism

conversion of one chemical species to another

-> metabolism of parent drug = elimination

elimination

irreversible loss of drug from the site of measurement through metabolism or excretion

primary organs of elimination

liver and kidney

excretion

irreversible loss of drug in the chemically unaltered form

disposition

drug distribution from systemic circulation to all tissues including organs of elimination

zero order

something is happening at a constant rate

not influenced by amount or conc of drug present

i.e. constant mass eliminated per unit time

first order reaction

rate changes with time depending on what is driving the process

rate changes but proportion of drug eliminated over time does not

i.e. rate = proportional to driving factor SO high conc = high elimination rate

zero order graph

conc vs time

-> get a straigh line

first order assumed conditions

instantaneous input + distribution

no: input, absorption or distribution phase

in first order kinetics why do we see decrease in conc over time

due to elimination

describe the first order kinetics graph

high conc at the start and therefore high elimination rate

as time goes on and elimination occurs we see a drop in concentrations

we see a slower elimination rate because of this

--> this can be described as an exponential decrease

in first order kinetics what do we get if we plot graph as log natural conc vs time

a straight line

compartment modelling

the use of hypothetical compartments to describe observed drug conc over time in the body

in compartments what are conc usually measured in

blood

plasma

when can a one compartment model be considered

if a drug is rapidly distributed to all tissues in the body

what determines the amount of drug in a one compartment at any time

rate of input into and elimination from the compartment

why may more than one compartment need to be added to the model

bcus often a drug will leave the central compartment through both elimination and distribution

in a multi compartment model how are distribution and elimination modelled

as first order processes

what does a compartment model determine

number of compartments which describe the drug distribution in the body

distribution kinetics between compartments

elimination from compartments

what do we need to know when looking at how the drug moves through the compartments

dose

conc of drug in blood

units of

- dose

- blood conc

- mass (mg)

- mass/volume

why do we need volume of distribution

dose measured in mass, conc measured in mass/volume

--> 2 different unit + need to connect in some way

volume of distribution

hypothetical volume used to link:

- the mass in the compartment at any time to conc measured at the time