Pharmacokinetics of drug absorption

1. Pharmacokinetics of Drug Absorption
Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D
Department of Pharmaceutics
Faculty of Pharmacy
Omer Al-Mukhtar University
Tobruk, Libya.
E-Mail: nanjwadebk@gmail.com
2014/02/22 1
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

2. CONTENTS
1. One compartment open model, Oral route.
2. Determination of absorption rate constant
(Plasma data, Urine data).
3. Extravascular multiple dose administration.
2014/02/22 2
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

3. One compartment open
model, Oral route
• Although this chapter will focus primarily on oral
dosing.
• In pharmacokinetics, the overall rate of drug
absorption may be described as either a first-order
or zero-order input process.
• Most pharmacokinetic models assume first-order
absorption unless an assumption of zero-order
absorption improves the model significantly or has
been verified experimentally
2014/02/22 3
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

4. Drug absorption
• Zero order process can be defined as the one whose
rate is independent of concentration of drug
undergoing reaction that is the rate of reaction
cannot be increased by further increase in
concentration of reactants.
• First Order process is the one whose rate is directly
proportional to concentration of the drug
undergoing reaction that is greater the concentration
faster the reaction.
2014/02/22 4
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

5. Zero-order absorption
model
One-compartment pharmacokinetic model for zero-order drug
absorption and first-order drug elimination.
2014/02/22 5
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

6. Zero-order absorption
model
• Zero-order drug absorption from the dosing site into the
plasma usually occurs when either the drug is absorbed
by a saturable process or a zero-order controlled-release
delivery system is used.
• The pharmacokinetic model assuming zero-order
absorption is described in this model, drug in the
gastrointestinal tract, DGI, is absorbed systemically at a
constant rate, k0.
• Drug is simultaneously and immediately eliminated from
the body by a first-order rate process defined by a first-
order rate constant, k.
2014/02/22 6
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

7. First-order absorption
model
One-compartment pharmacokinetic model for first-order drug absorption
and first-order elimination.
2014/02/22 7
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

8. First-order absorption
model
• Although zero-order absorption can occur,
absorption is usually assumed to be a first-order
process.
• This model assumes a first-order input across the gut
wall and first-order elimination from the body.
• This model applies mostly to the oral absorption of
drugs in solution or rapidly dissolving dosage
(immediate release) forms such as tablets, capsules,
and suppositories.
2014/02/22 8
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

9. Absorption and elimination
Model of drug absorption and elimination
DB =drug in body; VD = apparent volume of distribution
2014/02/22 9
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

10. Single oral dose
Plasma level–time curve for a drug given in a single oral dose. The drug
absorption and elimination phases of the curve are shown.
2014/02/22 10
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

11. Pharmacokinetic and
Pharmacodynamic
A typical plasma concentration-time profile showing pharmacokinetic and
pharmacodynamic parameters obtained after oral administration of single dose of
drug.
2014/02/22 11
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

12. Determination of absorption rate constant
(plasma data, Urine data)
• The absorption rate constant is determined by a
method known as “feathering,” “method of
residuals,” or “curve stripping.”
• From the plasma concentration versus time data
obtained or provided to you and the plot of the data
2014/02/22 12
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

13. Plasma data
Plasma level–time curve following administration of single
doses of (A) 250 mg, (B) 500 mg, and (C) 1000 mg of drug.
2014/02/22 13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

14. Urine data
Corresponding plots relating the plasma level–time curve
and the cumulative urinary drug excretion
2014/02/22 14
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

15. Plasma and Urine data
Corresponding plots relating the plasma level–time curve and
the cumulative urinary drug excretion.
2014/02/22 15
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

16. Plasma and Urine data
Corresponding plots relating the plasma level–time curve
and the rate of urinary drug excretion.
2014/02/22 16
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

17. Extravascular multiple dose
administration
2014/02/22 17
Faculty of Pharmacy, Omer Al-Mukhtar
University, Tobruk, Libya.

18. Extravascular single dose
administration
Typical plasma level–time curve for a drug given in a single
oral close
2014/02/22 18
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

19. THANK YOUE-mail: nanjwadebk@gmail.com
2014/02/22 19
Faculty of Pharmacy, Omer Al-Mukhtar
University, Tobruk, Libya.