PHARMACOKINETICS OF ORAL DRUG

ABSORPTION
Presented By-

 Humayan Kabir(14103079)
 Farhan Jamil (14103080)
 Zerin Tasnim(14103081)
 Masura Khatun(14103083)
 Anzam ul Islam(14103084)
 Khadija Tul Yeasmin(14103086)
 Breaking Down the Terms

Absorption rate constant: Absorption rate constant is the proportionality constant that
relates the rate of drug absorbed into the body. Pharmacokinetic samples collected around
Tmax are critical to describe the absorption characteristics of a drug

Elimination rate constant: The elimination rate constant K is a value used in

pharmacokinetics to describe the rate at which a drug is removed from the system. It is often
abbreviated K or Ke. It is equivalent to the fraction of a substance that is removed per unit
time measured at any particular instant and has units of T−1
 Significance of absorption and elimination rate
constant
 The rate of drug absorption represents the net results of the process, including
dissolution of the drug ,GI motility ,blood flow and transport of drug across capillary
membrane and into the systemic circulation
 The calculation of rate constant are useful in designing multiple dosage regimen
 Knowledge of the rate constant values allows for the prediction of peak and plasma drug
concentration following multiple dosage regimen
 In bioequivalence study drug products are given in chemically equivalent which can be
very useful in comparing the respective rates of absorption of a drug
 Determine Cmax
 Determine tmax
 Example of some maths

Problem:1
A single oral dose (100mg) of an antibiotic was given to an adult
male patient (43 years, 72kg). The volume of distribution for
this drug was 3L. From this literature, the pharmacokinetics of
this drug fit a one compartment open model. The equation that
best fits the pharmacokinetics of the drug is-
Cp=.45 (1-e-0.15t)

From the above equation, calculate-

(i) Plasma drug concentration after 4hours of drug intake.
(ii) t1/2 for the drug in this patient.
(iii) Absorption rate constant for the drug in this patient.

Assume, Cp is in µg/ml and the rate constant in hours-1.

Solution:
Here,
Cp=.45 (1-e-0.15t) ……(i)

The equation is similar to the equation of zero

order absorption kinetics-
Cp=Ko/K.VD(1-e-kt) …….(ii)

By comparing equation (i) and equation (ii),

we get-
Ko/K.VD=.45
And, K= 0.15
Solution:
(i) Here, t=4 hours
Cp= .45 (1-e-0.15x4)
= .203035 µg/ml
(Ans)

(ii) We know,
t1/2= 0.693/K
= 0.693/0.15
= 4.62 hour
(Ans)
Solution:

(iii) Here, Ko/K.VD=.45

And, VD= 3L
= 3000 ml
So, Ko=.45xK.VD
=.45x0.15x3000
= 202.5 hr-1
(Ans)
Problem:2  
An IV dose of 60 mg of an antibiotic was given to an adult male patient. From the literature,
pharmacokinetics of this drug fits one compartment open model. The equation that best fits the
pharmacokinetics of the drug,
=40(1-)
If the absorption & elimination rate constant ratio is 0.7,calculate the value of

Solution:
Here, =0.7 ; k =1.2 ; =?
Now, we know zero order equation,
)
or,
Given equation, =40(1-)
so, from comparing two equation we get,
=40
or,.0.7 =40
or,= = 0.0175 μg/ml (Ans.)
Problem:3

•drug  fits one compartment open model & follows first order absorption. If =1.2, k = 1.05 &
A single oral dose of 100 mg paracetamol was given to an adult female patient. Pharmacokinetics of the

bioavailability is 89% ,calculate after 3 hrs.

Solution:
Here, = 1.2 , k =1.05 , t = 3 hrs , = 100 mg
Bioavailability (F) = 89% = = .89, =?
From first order absorption equation,
= (-)
or, = (-) (We know, = . )
= ( -)
=7120.0155
= 11.036 mg (Ans.)
Problem:4
A single oral dose (100mg) of an antibiotic was given to an
Adult male patient (43 years, 72kg). Half life was 4.76 hour. From
This literature, the pharmacokinetics of this drug fit a one
compartment open model. The equation that best fits the
pharmacokinetics of the drug is-
Cp=45 (e-kt -e-1.5t)

From the above equation, calculate-

(i) K
(ii) tmax
(iii) Cmax

Assume, Cp is in µg/ml and the rate constant in hours-1.

Solution:
The general equation for a one compartment open model with oral absorption
is-
Cp= (F.Ka.DO)/VD (Ka-K) (e-kt-e-Kat)

Given,
Cp=45 (e-kt -e-1.5t)

Now, by comparing both the equation we get-

Ka=1.5 hr-1
(F.Ka.DO)/VD (Ka-K) = 45
t1/2= 4.76hour

(i) K= 0.693/ t1/2

= 0.693/4.76
= 0.14558 hr-1
(Ans)
Solution:

(ii) tmax = (ln Ka/K)/( Ka-K)

= (ln 1.5/0.14558)/(1.5-0.14558)
= 1.722 hr
(Ans)

(iii) Cmax= (F.Ka.DO)/VD (Ka-K) (e-ktmax-e-Katmax)

= 45 (e-0.14x1.72-e-1.5x1.72)
=31.62228 µg/ml
(Ans)
 Problem:5
A single oral dose (100mg) of an antibiotic was given to an
adult male patient (43 years, 72kg). From this literature,
the pharmacokinetics of this drug fit a one compartment
open model. The equation that best fits the pharmacokinetics of
the drug is-
Cp=45 (e-0.17t -e-1.5t)
From the above equation, calculate-
(i) Plasma drug concentration after 4hours of drug intake.
(ii) t1/2 for the drug in this patient.
(iii)Volume of distrubution
Assume, Cp is in µg/ml and the rate constant in hours-1
And this model is 9o% bioavailable
Solution:
The general equation for a one compartment open model with oral absorption
is-
Cp= (F.Ka.DO)/VD (Ka-K) (e-kt-e-kat)

Given,
Cp=45 (e-0.17t -e-1.5t)

Now, by comparing both the equation we get-

Ka=1.5 hr-1

K=0.17 hr-1
(F.Ka.DO)/VD (Ka-K) = 45
(i) Here, t=4 hours
Cp= 45 (e-0.17x4-e-1.5x4)
= 22.686 µg/ml (Ans)
Solution:

(ii) We know,
t1/2= 0.693/K
= 0.693/0.17
= 4.076 hour
(Ans)

(iii) Here, (F.Ka.DO)/VD (Ka-K) =45

And, VD= (F.Ka.DO)/45 (Ka-K)
So, VD =.9x1.5 x100/45(1.5-.17)
=2.2556 ml
(Ans)
Problem:6
Two drugs, A and B have the following pharmacokinetic
parameters after a single oral dose of 400mg.

Both drugs follows a one compartment pharmacokinetic

model and are 90% bioavailable.

(i) Calculate the tmax for each drug.

(ii) Calculate the Cmax for each drug.
Solution:

(i) Here, For drug A,

Ka =1 hr-1
t1/2 =3 hr

So, K= 0.693/ t1/2

= 0.693/3
= 0.231

So, tmax for drug A= (ln Ka/K)/( Ka-K)

= (ln 1.0/0.231)/( 1.0-0.231)
= 1.905 hr
(Ans)
Solution:

Here, For drug B,

Ka =0.2 hr-1
t1/2 =4 hr

So, K= 0.693/ t1/2

= 0.693/4
= 0.173

So, tmax for drug B= (ln Ka/K)/( Ka-K)

= (ln 0.2/0.173)/(0.2-0.173)
= 5.4 hr
(Ans)
Solution:
(ii) Here, For drug A,
Bioavailability= 90%
Fraction of drug absorbed systemically, F= 0.9
Dose, Do= 400mg
= (400x1000) µg
=400000 µg
Volume of distribution, VD= 10000ml
tmax= 1.905 hr
Ka =1.0 hr-1
K =0.231 hr-1

So, Cmax for drug A,

Cmax= (F.Ka.DO)/VD (Ka-K) (e-ktmax-e-Katmax)
= (0.9x1x400000)/[10000 (1-0.231)] (e -0.231x1.905-e-1x1.905)
= 23.18 µg/ml
(Ans)
Solution:
Here, For drug B,
Bioavailability= 90%
Fraction of drug absorbed systemicallu, F= 0.9
Dose, Do= 400mg
= (400x1000) µg
=400000 µg
Volume of distribution, VD= 20000ml
tmax= 5.4 hr
Ka =0.2 hr-1
K =0.173 hr-1
So, Cmax for drug B,
Cmax= (F.Ka.DO)/VD (Ka-K) (e-ktmax-e-Katmax)
= (0.9x0.2x400000)/[20000 (0.2-.173)] (e-.173x5.04-e-0.2x5.04)
= 7.12 µg/ml
(Ans)