4. Pharmacokinetics Flashcards by J Y

what is pharmacokinetics

study of concentration time profile of a drug in the body

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what principles does pharmacokinetics encompass and quantitate

absorption
distribution
metabolism
excretion

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what does the absorption and elimination look like on the plasma conc over time graph

sharp increase in plasma conc = absorption

elimination so experiences decreases

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why do we use plasma conc to measure drug conc

blood moves drug around the body so can assume there is a relationship between the conc of drug in plasma and that in the target receptor

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at what state does the plasma conc gives relatively good index of conc at the receptor

steady state

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is there more variation between conc and effect or betw dose and effect

more betw dose and effect

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what is the conc time curve after oral dosing area signify

extent of absorption of drug

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once what limit is reached does the pharmacological response begin

minimum effective conc

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what is the difference in the plasma conc time graph for IV and oral delivered drugs

same drug and same dose but give by diff routes

what is the diff is if any with IV and oral for rate of elimination and dose level

oral = initial increase for absorption and decrease as eliminated

IV = all drug enters plasma so no absorption phase and then eliminated from body

oral dose rate of elimination is the same once reached systemic circulation as its the same drug so will be distributed to same compartment and eliminated the same way

not all dose reaches systemic circulation so plasma conc for oral dose is less than that of IV dose

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what is the oral bioavailability

not all drug reaches the systemic circulation after oral dosing due to partial absorption and first pass metabolism

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what does bioavailibilty reflect

fraction of dose that reaches the systemic circulation

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what is the equation for bioavailibility

F = (AUCpo/AUCiv) x (doseiv/dosepo)

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ideally F should be what percentage to be given orally

more than 20%

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if F is too low what does that indicate

that the drug is ineffective way of delivering drugs

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what is AUC po or AUC iv

area under curve

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what is the unit for dose

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what is the unit for F

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if you want drug exp to be same for oral and iV, what happens to the bioavailb equation

areas under curve for oral and IV should be equal and therefore =1 so can take that away from equation just to give F=IV dose/oral dose

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what parameter is drug distribution defined by

volume of distribution

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what is the equation for volume of distribution

VD = amount of drug in body/plasma drug conc

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what is the volume of distribution determined by

6 things

body mass and composition
tissue blood flow
tissue blinding
plasma protein binding
physico-chem properties of drug
natural barriers

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how does the tissue binding affect the volume of distribution

tissue binding increases volume of distribution

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how does the plasma protein binding affect the volume of distribution

plasma binding limits drug distribution to tissue so has an opposing effect to drug distribution

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what is the bathtub model for the volume of distribution

non sponge example

drug fully dissolved and take sample of water and measure drug conc in sample

calculate the volume of distribution using equation

volume of distribution calculated corresponds with the actual volume of water in bathtub

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what is the bathtub model for the volume of distribution sponge example

dissolve drug in same bathtub but this time you take another sample of water and measure conc but this time conc is lower than non sponge example and after the VD equation the volume in bathtub is calculated to be way larger than expected volume must be something that binds drug and allows drug to hide so isnt measured with recorded (eg 90% bound to sponge so only leaves 10% of dose to be freely measured in water)

large hydrophilic drugs will stay in what volume of fluid in the body what does that say in terms of volume of distribution

in plasma expect volume of distribution to be close to value of plasma volume

what does it mean when the volume of distribution is too big

drug is hiding in body where its not recorded and is stored in fat as lipophilic so not circulating in plasma

is the volume of distribution a actual volume

no its a hypothetical

drugs with high molecular weight is restricted to what body fluid compartment why

bind extensively to plasma proteins and volume of distribution is close to volume of plasma as it is bound to it and cant move out of it

drugs with low molecular weight and hydrophilic is restricted to what body fluid compartment why

can move out of plasma as capillary are porous but hydrophilic so cant cross cell membrane and limited to extracellular compartment

smaller and larger volume of distribution is more likely to be bound to what compartments

Smaller volume of distribution more likely drug is bound to plasma compartment, larger the volume of distrib means more likely drug us bound to tissues or fat

what is the loading dose

administered to achieve a target conc rapidly

what is the loading dose dependent on

volume of distribution

what does loading dose do to help reach target conc

helps fill volume of distribution faster to rapidly achieve the target conc

the bigger the volume of distribution what happens to the dose req to reach target conc

higher dose

what is the equation for loading dose

loading dose (mg) = VD (L) x target conc (mg/L)

if no loading dose is used, what happens to the VD and time taken to reach target conc

volume takes time to fill up so the larger the VD the longer the time to reach target conc

what is the loading dose usually given as and what effect does this have on target conc

usually given as a IV bolus so that target conc is reached quickly

how is the target conc maintained

by IV infusion but oral loading doses can also be used

what is drug elimination defined by - ie which parameter

clearance

what is clearance

describes relationship between drug conc and rate of elimination of drug from body

what is the clearance equation

clearance (L/h) = elimination rate (mg/h)/conc (mg/L) clearance = dose/AUC

what is clearance plasma

sum of clearance from individual organ CLplasma = CLrenal + CLhepatic + CLothers

why is clearance and rate of elimination arent the same

clearance is a unit of flow and elimination describes rate of loss

in the bathtub model what is the equivalent of the clearance and conc of drug in plasma

plughole = clearance height = conc of drug in plasma

what is the first order process of clearance relationship between rate of elimination and drug conc what is the assumption

amount of drug eliminated or rate of elimination is proportional to drug conc so there is a linear relationship between rate of elimination and drug conc

in the first order process what happens with higher conc

the higher the conc the more drug is presented to tissues for elimination

is the clearance independent of conc and what does this mean for proportionality

independent so is proportionality constant = constant value of ratio betw 2 proprtional quantities (rate of elimination and conc)

what is the maintenance dose rate what does this mean for dose rate and rate of elimination

dose rate to achieve and maintain a target conc = steady state conc dose rate = rate of elimination

steady state conc can be achieved by what 2 methods

IV infusion or repeated oral dosing

what is the equation for maintenance dose

maintenance dose (mg/h) = clearance (L/h) x target conc (mg/L)

a rapidly cleared drug will need a large/small maintenance dose to keep drug conc at target levels

larger

what is the steady stat conc

when dose rate in equals rate of elimination so no net change in conc

what is the half life of a drug

time required for drug concentration to fall by half

what does the half life of a drug depend on

volume of distribution and clearance

what is the equation for drugs half life

T1/2 = 0.7 x VD/CL

if the half life is known what 2 things can be estimated

how much drug is left in the body how long it will take to reach steady state

what causes the accumulation of drug

repeated dosing or infusion, drug accumulates in body until input rate = elimination rate

when does steady state occurin terms of accumulation

when drug accumulation is complete and conc have plateaued

the time required to reach steady state is related to what parameter

half life

accumulation >90% is complete after how many half lives

4 half lives

steady state is reached after how many half lives generally

4-5 half lives

if the wait is more than 5 half lives before re administration what happens to drug

drug will not accumulate as most will have been eliminated already

what is needed for the drug conc to increase until it reaches the plateau

continue to administer same dose at every half life time interval

what will happen to the drug in drug accumulation

increase by half

what is the time to reach steady state can it be be reduced by increasing dose

drug with a long half life will take a long time to reach steady state cannot be reduced by increasing dose

increasing the dose does what to the steady state and is half life affected

increases steady state conc half life not affected by dose

what can shorten the time to reach steady state

loading dose using several loading dose can reach steady state quicker and maintain it by giving continuous infusion following loading doses

time taken to reach steady state is the sum of what

elimination of loading bolus and maintenance infusion

what are the 2 models of pharmacokinetics

1 and 2 compartment models

what are compartment models and why do we use them

time course of drug in body and dictated by processes of ADME

what is the 1 compartment model and what are the assumptions

assume well stirred compartment with instantaneous mixing linear pharmacokinetics where elimination is a first order process

does the 1 compartment model predict drug conc in tissues of the body, what does it assume and what is the curve shape of it on a graph

Does not predict actual drug conc in various tissues of body but assumes drug conc is proportional that what is measured in plasma Log linear curve for log conc over time

what is the 2 compartment theory

distribution and elimination first stage is fast due to instant mixing in central compartments incl tissues that are well perfused followed by slower distribution to other tissue such as muscle/fat assumes elimination is from drug returned to plasma compartment and delivered to organs that eliminates drugs so this 2nd process is a bit slower

what does the graph look like for the 2 compartment theory

biexponential curve on log scale