Transcript Pharmacokinetics of Drug Administered by Intravenous Route Dr. Basavaraj K. Nanjwade M. Pharm., Ph.

Pharmacokinetics of Drug
Administered by Intravenous Route
Dr. Basavaraj K. Nanjwade
M. Pharm., Ph. D
Department of Pharmaceutics
Faculty of Pharmacy
Omer Al-Mukhtar University
Tobruk, Libya.
E-Mail: [email protected]
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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CONTENTS
1. One compartment open Model in I. V.
Injection(Bolus).
2. Two compartment open Model in I. V.
Injection(Bolus).
3. Intravenous administration, Multiple dosing.
4. References.
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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One compartment
open Model in I. V. Injection
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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One compartment
open Model
The one compartment open model is the simplest
model:
1. The body is considered as a single, kinetically
homogeneous unit that has no barriers to the
movement of drug.
2. Final distribution equilibrium between the drug in
plasma and other body fluids (i.e. mixing) is
attained instantaneously and maintained at all
times. This model thus applies only to those drugs
that distribute rapidly throughout the body.
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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One compartment
open Model
3. Drugs move dynamically, in (absorption) and out
(elimination) of this compartment.
4. Elimination is first-order (monoexponential) process
with first-order rate constant.
5. Rate of input (absorption)>rate of output (elimination).
6. The anatomical reference compartment is plasma and
concentration of drug in plasma is representative of
drug concentration in all body tissues i.e. any change in
plasma drug concentration reflects a proportional
change in drug concentration throughout the body.
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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One compartment
open Model in I. V. Injection
• Body before and after a rapid I.V. bolus
injection, considering the body to behave as a
single compartment. In order to simplify the
mathematics it is often possible to assume
that a drug given by rapid intravenous
injection, a bolus, is rapidly mixed. This slide
represents the uniformly mixed drug very
shortly after administration.
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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One compartment
open Model in I. V. Injection
Schematically, one compartment model can be
represented as:
kel
Drug in
Body
Drug
Eliminated
Xp = Vd • C
Where Xp is the amount of drug in the body, Vd is the
volume in which the drug distributes and kel is the first
order elimination rate constant
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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One compartment
open Model in I. V. Injection
• The one-compartment model does not predict
actual drug levels in the tissues, but does
imply that changes in the plasma levels of a
drug will result in proportional changes in
tissue drug levels.
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Two compartment
open Model in I. V. Injection
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Two compartment
open Model
The commonest of all multicompartment model is a twocompartment model. In such a model, the body tissues are
broadly classified in 2 categories:
1. Central Compartment or Compartment 1 comprising of
blood and high perfused tissues like liver, lungs, kidney,
etc. that equilibrate with the drug rapidly. Elimination
usually occurs from this compartment.
2. Peripheral or Tissue Compartment or Compartment 2
comprising of poorly perfused and slow equilibrating
tissues such as muscles, skin, adipose, etc. and considered
as a hybrid of several functional physiological units.
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Two compartment
open Model in I. V. Injection
• Intravenous bolus injection with a two compartment
model.
• Often a one compartment model is not sufficient to
represent the pharmacokinetics of a drug.
• A two compartment model often has wider application.
• Here we consider the body is a central compartment with
rapid mixing and a peripheral compartment with slower
distribution.
• The central compartment is uniformly mixed very shortly
after drug administration, whereas it takes some time for
the peripheral compartment to reach a pseudo equilibrium.
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Two compartment
open Model in I. V. Injection
Blood,
kidneys,
liver
Drug in
Central
Compartment
K 12
Drug in
Peripheral
Compartment
K 21
kel
Fat, muscle
Drug
Eliminated
For both 1- and 2-compartment models, elimination
takes place from central compartment
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Intravenous administration
IV: Intravenous,
2014/02/22
IM: Intramuscular,
SC: Subcutaneous
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Multiple dosing
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Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Multiple dosing
• Multiple dose curves with slow, medium, and fast
excretion. Alteration of drug elimination is
particularly important when drugs are given
repeatedly. If it is assumed that the drug is
eliminated normally when in fact it is slowly
eliminated, drug accumulation may occur with toxic
concentrations
reached.
Alternately
faster
elimination than expected may cause sub
therapeutic concentrations to be reached.
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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References
1. Principles of Pharmacokinetics Pharmacokinetics of
IV Administration, 1-Compartment by Karunya
Kandimalla.
2. Based on A First Course in Pharmacokinetics and
Biopharmaceutics by David Bourne, College of
Pharmacy, University of Oklahoma.
3. Biopharmaceutics and pharmacokinetics by D.M
Brahmankar and Sunil. B. Jaiswal.
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Thank YOU
E-mail: [email protected]
2014/02/22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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