Pharmacokinetics of drug administered by intravenous route

Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D

Department of PharmaceuticsFaculty of Pharmacy

Omer Al-Mukhtar UniversityTobruk, Libya.

E-Mail: nanjwadebk@gmail.com

2014/02/22 1Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

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 2Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

One compartment open Model in I. V. Injection

2014/02/22 3Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

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 4Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

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 5Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

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 6Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

One compartment open Model in I. V. Injection

Drug in Body

Drug Eliminated

Xp = Vd • C

kel

Schematically, one compartment model can be represented as:

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 7Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

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 8Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

Two compartment open Model in I. V. Injection

2014/02/22 9Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

Two compartment open Model

The commonest of all multicompartment model is a two-compartment 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 10Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

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 11Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

Two compartment open Model in I. V. Injection

Drug in Central

Compartment

Drug Eliminated

Drug in Peripheral

Compartment

kel

Blood, kidneys,

liver

Fat, muscle

K 12

K 21

For both 1- and 2-compartment models, elimination takes place from central compartment

2014/02/22 12Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

Intravenous administration

IV: Intravenous, IM: Intramuscular, SC: Subcutaneous

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Multiple dosing

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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 15Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

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.

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Thank YOUE-mail: nanjwadebk@gmail.com

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