Factors affecting the drug cone-time profile (Cont'd)
c- Total body clearance
Examine the drug conc-time profiles after iv administration of the same dose of different drugs that have the same Vd and different total body clearance.
Larger total body clearance results in faster rate of decline in the plasma conc-time profile if Vd is constant.
Example:
In children, the average pharmacokinetic parameters of theophylline are: k=0.15 hr-1 and Vd = 0.5 L/kg, while in adults k = 0.1 hr-1 and Vd = 0.5 L/kg. Which of the two patient populations will have the plasma concentration above the MEC for longer duration after administration of similar doses of theophylline (adjusted for body weight)
Since children eliminate theophylline at faster rate, theophylline concentration will stay above the MEC for shorter time compared to in adults. Adults will have theophylline concentrations above MEC for a longer period of time.
- Administration of the same doseof different drugs that have different CLT will result in different rates of decline of the plasma concentration, if Vd is similar.
- The plasma cone of drugs that have higher CLT will decline at a faster rate (larger k and shorter t1/2).
-Changes in CLT will cause a change k, t1/2 and AUC, however it will not affect Cpo.
Parameters
Dis the dose of the drug (amount).
CLTis the total body clearance (volume/time).
Vdis the volume of distribution (Volume).
Volume of distribution
The volume of distribution is the apparent volume in which the drug can be distributed in. It is the factor that relates the amount of drug in the body to the concentration of the drug in the sampling site. It is not an actual volume, however it is a hypothetical volume determined by the drug distribution behavior.
The volume of distribution ranges from 3-5 liters to more than 25 L/kg. Drugs with higher affinity for tissues, have higher volume of distribution.
Total body clearance (CLT)
The total body clearance is the volume of the plasma or blood which is completely cleared from the drug per unit time. It has units of volume/time.
The CLT for a drug is constant within a patient (dose and concentration independent) when the elimination processes follow first-order kinetics.
The total body clearance is a measure of the efficiency of all eliminating organs in eliminating the drug and it is the sum of all organ clearances (i.e. CLT is the sum of the renal clearance, hepatic clearance and all other organ clearances).
The elimination rate constant and the half life (the dependent pharmacokinetic parameters) are dependent on (is determined from) the total body clearance and the volume of distribution (the independent pharmacokinetic parameters).
