Key Pharmacokinetic Calculations

7/29/2019 Key Pharmacokinetic Calculations

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KEY PHARMACOKINETIC

CALCULATIONS


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We can calculate this in two ways:

(1) Graphically by determining the time forthe drug concentration to fall by 50% (usingthe plot of log conc of drug vs. time)

(2) t/2 = 0.693/kelt/2 = 0.7/kel

DETERMINATION OF HALF-LIFE OF A DRUG


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CLEARANCE OF DRUGS Clearance (Cl) of a drug is defined as:

the volume of a biological fluid(generally plasma) from which that drug isremoved ("cleared") per unit of time

(usually per minute or per hour).

Clearance may also be written as:

Clt= Kel.Vd(remember that t1/2 = 0.7/kel)

and that kel

= 0.7/ t1/2

)

thus Clt= (0.7/t1/2).Vd

Thus clearance can be thought as the fraction of

the Vd from which the drug is removed in a unitof time.


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FIRST-ORDER KINETICS

PRINCIPLE

The half-life of elimination of a drug (and

its residence in the body) depends on its

clearance and its volume of distribution

t1/2 is proportional to Vd

t1/2 is inversely proportional to CL

t1/2

= 0.7 x Vd/CL


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CALCULATION of a LOADINGDOSE

We need to know the plasma concentration wewant to achieve (TCpl)

This will be distributed into the Vd

THUS loading dose(i.v.) = TCpl x Vd

BUT remember that this is OK for i.v. routeonly!! if we give a loading dose orally then we needto take into account its bioavaiability

then loading dose(oral) = TCpl x Vd / F


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CALCULATION of a MAINTENACEDOSE

We need to know the plasma concentration wewant to achieve (TCpl)

AND we need to know how fast it is cleared!!

THUS dosing rate(i.v.) = TCpl x ClBUT remember that this is OK for i.v. routeonly!! if we are giving the drug orally then we need

to take into account its bioavaiability

then dosing rate(oral) = TCpl x Cl/ F


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CALCULATION of a MAINTENACEDOSE (contd.)

Remember to check the units used!! Preferably use Cl in l/hr andTCpl in mg/L

How often will the drug be given (in hr) ?

Maintenance Dose

= Dosing Rate/F x Dosing Interval= TCpl x Cl / F x Dosing Interval


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PHARMACOKINETIC PARAMETERS

Volume of distributionVd = DOSE / C0

Half-life t1/2 = 0.7 / Kel

Plasma clearance Cl = Kel .Vd

Bioavailability (AUC)x / (AUC)iv


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EXTENSIONS of these EQUATIONS

Volume of distributionVd = DOSE/C0 C0 = DOSE/Vd

Half-life t1/2 = 0.7/KelKel = 0.7/t1/2

Plasma clearance Cl = Vd x KelCl = V

dx

0.7/t

1/2

Vd = Cl x t1/2/0.7 t1/2 = Vd x 0.7/Cl

Bioavailability F = (AUC)x / (AUC)iv


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LOADING & MAINTENANCE DOSES

Loading Dose= TCpl x Vd / F

Maintenance Dose

= Dosing Rate / F x Dosing Interval

= TCpl x Cl / F x Dosing Interval

Key Pharmacokinetic Calculations

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