One compartment open model

Clearance
Clearance represents the capacity for drug removal by

various organs and is defined as the volume of blood

from which all drug is removed per minute (mL/minute).

Drugs can be cleared through numerous pathways. However, most drugs

are cleared by some combination of renal clearance (ClR), hepatic

clearance (ClH), and biliary clearance (ClB). The total systemic clearance

of a drug (ClT) is the sum of all clearances by various mechanisms.

 Assessment of pharmacokinetic parameters after
administration of a drug as IV infusion

Ro KE

zero order infusion

Rate of change of drug = Rate of drug input- Rate of drug output

dX/dt = Ro - KE.X

Integrating and rearranging above equation from t 0 t and

for X0 X;

X= Ro (1- e –K .t)
E
1
KE
 Since, X= C. Vd
C= Ro (1- e –KE.t)
KE. Vd 2

Since drug is continuously infused; after some time from the start
of the infusion, the rate of infusion equals the rate of elimination
and steady state is attained.
Therefore at steady state, i.e. Css;

Ro= KE.X
Ro= KE. Css.Vd
Css = Ro
3
KE. Vd

Equation 2 at Css becomes,

 C= Css. (1- e –KE.t) 4
Rearrangement yields,
Css- C = e –KE.t
Css

log Css- C = - KE.t 5

Css 2.303
Vd= Xo/Co

t1/2= 0.693/KE

Cl= KE. Vd
 Significance of loading dose
loading dose : It is a high initial dose of a drug that is given to enable
its therapeutic level in the bloodstream to be reached quickly. The
loading dose is subsequently reduced to a lower maintenance dose.
Recalling once again, X=C.Vd

XoL =Css.Vd

Also, we have proved at steady state conc,

Css = Ro
KE. Vd
Therefore, XoL = Ro
2
KE
When drug is administered as IV bolus followed by IV
infusion as maintenance dose; then C at anytime before
Css is reached,
C= XoL (1- e –KE.t) + Ro (1- e –KE.t)
3
Vd KE. Vd
References:
1. APPLIED BIOHARMACEUTICS AND PHARMACOKINETICS BY

LEON SHARGEL.

2. BIOHARMACEUTICS AND PHARMACOKINETICS A TREATISE

BY BRAHMANKAR JAISWAL.