KEY PHARMACOKINETIC CALCULATIONS

DETERMINATION OF HALFLIFE OF A DRUG

We can calculate this in two ways: (1) Graphically by determining the time for the drug concentration to fall by 50% (using the plot of log conc of drug vs. time) (2) t/2 = 0.693/kel t/2 = 0.7/kel

CLEARANCE OF DRUGS
Clearance (Cl) of a drug is defined as: the volume of a biological fluid (generally plasma) from which that drug is removed ("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 unit of time.

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

CALCULATION of a LOADING DOSE We need to know the plasma concentration we

want 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. route only!! if we give a loading dose orally then we need to take into account its bioavaiability then loading dose(oral) = TCpl x Vd / F

CALCULATION of a MAINTENACE DOSE We need to know the plasma concentration we

want to achieve (TCpl) AND we need to know how fast it is cleared!! THUS

dosing rate(i.v.) = TCpl x Cl

BUT remember that this is OK for i.v. route only!! if we are giving the drug orally then we need to take into account its bioavaiability

then

dosing rate(oral) = TCpl x Cl / F

CALCULATION of a MAINTENACE DOSE (contd.)

Remember to check the units used!! Preferably use Cl in l/hr and TCpl 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

PHARMACOKINETIC PARAMETERS
Volume of distribution Vd = DOSE / C0 Half-life Plasma clearance t1/2 = 0.7 / Kel Cl = Kel .Vd (AUC)x / (AUC)iv

Bioavailability

EXTENSIONS of these EQUATIONS

Volume of distribution

Vd = DOSE/C0
Half-life

C0 = DOSE/Vd

t1/2 = 0.7/Kel
Kel = 0.7/t1/2

Plasma clearance Cl = Vd x Kel Cl = Vd x 0.7/t1/2 Vd = Cl x t1/2/0.7 t1/2 = Vd x 0.7/Cl

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

LOADING & MAINTENANCE DOSES

Loading Dose = TCpl x Vd / F Maintenance Dose = Dosing Rate / F x Dosing Interval = TCpl x Cl / F x Dosing Interval