Online lecture of 13th week

Date: Monday, 6th July, 2020

Contents
 Superposition Principle.

 Repetitive intravenous injections.

 Drug clearance (Chapter 6)

Principle of Superposition
• superposition principle also known as overlay principle.
• For calculation of multiple-dose regimens, it is necessary to decide
whether successive doses of drug will have any effect on the previous
dose or not.
• Superposition principle assumes that early doses of drug do not affect the
pharmacokinetics of subsequent doses.
OR
• It states that “the 2nd dose will not change the pharmacokinetics of the
1st dose
Basic assumptions of superposition principle.
(1) that the drug is eliminated by first-order kinetics and
(2) that the pharmacokinetics of the drug after single dose (first dose) are not
altered after taking multiple doses.
Benefit
• Superposition principle help the pharmacokineticist to project the plasma drug
concentration– time curve of a drug after multiple consecutive doses based on
the plasma drug concentration–time curve obtained after a single dose.
• If we know dose, half life and VD of a drug then we can calculate the
concentration of drug at anytime according to superposition principle
Example:
320mg of a drug with 100% bioavailability is provided orally whose VD is 10L
and half life is of 4 hrs. What will be concentration in the blood at any hour?
Limitations
This principle can’t be applied to conditions like:
• Non-Linear Pharmacokinetics,
• Pathophysiological Conditions,
 saturation of a drug carrier system,
 enzyme induction,
 and enzyme inhibition.
 Repetitive intravenous injections.
• In severity and in emergency situations for the maintenance of the drug
concentration into the systemic circulation I/V route is used (100%
bioavailability)
• For maintenance of the drug concentration in body dose and interval should
be adjusted properly
There are two types of concentrations:
• DB(Total Body Concentration in the body)
• Cp Blood (Concentration only in blood/plasma)
Following parameters can be calculated easily:
• Total Concentration in the body
• Maximum Concentration in the body
• Minimum Concentration in the body
• Average Concentration in the body
Formula:

Where;
K = rate of elimination
DB = Drug concentration in the body
D0 = Dose
t = Dosage interval
e = base of ln (natural log)
minus symbol shows elimination/excretion
• To provide next dose the previous remaining concentration must be known

Dose concentration remaining from previous dose (f)

If (f) = 1 then 100%
If (f) = 0.9 then 90% and so on i.e. f = 0.25 = 25%

• For the calculations the value of k is different for 1st Order and 0th order
reactions i.e.
 For 1st Order k = 0.693/half life

 For 0th Order k = 0.5/half life

 Or by rearranging:
Half life = 0.693/k or 0.5/k
Data’
D0 = 1000mg, t1/2 = 3 hrs. VD = 20 L, t = 6 hrs.
Calculate
• Cmax, Cmin and Cav in body.
• Cmax, Cmin and Cav in plasma.
Drug clearance (CLT).
It is pharmacokinetic term. Removal of drug without any mechanism or
identification of mechanism
Definition (Theoretical Definition)
“Fixed volume of blood/fluid containing drug, cleared of drug per unit time is
known as CLT” (Theoretical Definition)
Definition (Practical Definition)
“Ratio of the Rate of elimination and plasma drug concentration is known as CLT”
(Practical Definition)

OR

But Cp = OR DB = Cp x Vd So,

By putting equation (2) into (1) we get,

CLT= KVD
o Example:

 CLT­­ of Penicillin is 15ml/min and Vd = 12L (12000ml) so it means

from 12000ml Vd the 15ml is cleared per minute

 Drug x’s CLT is 15ml/min, Cp is 2mcg/ml then its Rate of

elimination can be calculated as:

 For same the CLT can be:

Thanks