One Compartment Open Model

(Intravenous Bolus Administration)

Prepared By:
Ms. Suman R. Borsadiya
Assistant Professor
Faculty of Pharmacy, Marwadi University
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✓ When a drug that distributes rapidly in the body is given in the form
of a rapid intravenous injection (i.e. I. V. bolus or slug), it takes
about 1 - 3 minutes for complete circulation & so the rate of
absorption is neglected in calculations.

✓ The model can be depicted as follows:

Blood & Other

KE
Body Tissues

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✓ The general expression for rate of drug presentation to the body is:
dX/dt = Rate in (Availability) - Rate out (Elimination) -----Eq. 1
✓ Since Rate in or absorption is absent, the equation becomes:
dX/dt = - Rate out -----Eq. 2
✓ If the Rate out or Elimination follows 1st order kinetic, then:
dX/dt = -KEX -----Eq. 3
Where, KE = 1st order elimination rate constant
X = amount of drug in body at any time t remaining to be eliminated
Negative sign indicates that the drug is being lost from the body.
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✓ The various related pharmacokinetic parameters can now be
estimated.
I. Elimination Rate Constant:
✓ For a drug that follows one compartment kinetics & administered
as rapid I. V. injection, the decline in plasma drug concentration is
only due to elimination of drug from the body, the phase being
called as elimination phase.
✓ Elimination phase can be characterized by 3 parameters i.e.
elimination rate constant, elimination half life & clearance.
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• Eq. 7 is that of a straight line & indicates that a semi logarithmic
plot of log C versus t will be linear with y intercept log Co.

• The elimination rate constant is directly obtained from the slope of

the line.

• It has unit of min-1.

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• Thus, a linear plot is easier to handle mathematically than a curve
which in this case will be obtained from a plot of Concentration
versus t on a regular (Cartesian) graph paper.

• Thus, Co, KE & t1/2 can be readily obtained from log concentration
versus t graph.

• The elimination or removal of the drug from the body is the sum of
urinary excretion, metabolism, biliary excretion, pulmonary
excretion & other mechanisms involved therein.
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• Thus, KE is an additive property of rate constants for each of these
processes & better called as Overall Elimination Rate Constant.
KE = Ke + Km + Kb + Kp + …. -----Eq. 8
• The fraction of drug eliminated by a particular route can be
evaluated if the number of rate constants involved & their values are
known.
• Eg., if a drug is eliminated by urinary excretion & metabolism only,
the fraction of drug excreted unchanged in urine Fe & fraction of
drug metabolized Fm can be given as follow:
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 Fe = Ke/KE -----Eq. 9

Fm = Km/KE -----Eq. 10

II. Elimination Half Life (Or Biological Half Life):

• It is the oldest & the best known of all pharmacokinetic parameters

& was once considered as the most important characteristic of a
drug.

• It is defined as the time taken for the amount of a drug in the body
as well as plasma concentration to decline by ½ or 50% its initial
concentration. 11
• It is expressed in hours or minutes.

• Half life related to elimination rate constant by the following Eq.

t1/2 = 0.693/KE -----Eq. 11

• Today, increased physiologic understanding of pharmacokinetic

shows that half life is a secondary parameter that depends upon the
primary parameters i.e. clearance & apparent volume of distribution
according to the following Eq.

t1/2 = (0.693 × Vd) / ClT -----Eq. 12

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Apparent Volume of Distribution:

• Clearance & apparent volume of distribution are two separate &

independent pharmacokinetic characteristics of a drug.

• Since, they are closely related with the physiologic mechanisms in

the body, they are called as primary parameters.

• Apparent volume of distribution is defined as follow:

-----Eq. 13
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• Vd is a measure of the extent of distribution of drug & is expressed
in litres.

• The best & the simplest way of estimating Vd of a drug is

administering it by rapid I. V. injection & using the following Eq.

Vd = Xo/Co = I. V. bolus dose / Co -----Eq. 14

• Eq. 14 can only be used for drugs that obey one compartment
kinetics.

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• This is because the Vd can only be estimated when distribution
equilibrium is achieved between drug in plasma & that in tissues & such
an equilibrium is established instantaneously for a drug that follows one
compartment kinetics.

• A more general, more useful non compartmental method that can be

applied to many compartment models for estimating the Vd is:

For drugs given as I. V. Bolus, Vd = Xo/[KE.AUC] -----Eq. a

For drugs administered extravascularly (Orally),

Vd = FXo /[KE.AUC] -----Eq. b

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Clearance:

• Clearance is the most important parameter in clinical drug

applications & is useful in evaluating the mechanism by which a
drug is eliminated by the whole organism or by a particular organ.

• Just as Vd is needed to relate plasma drug concentration with

amount of drug in the body, clearance is a parameter to relate
plasma drug concentration with the rate of drug elimination
according to the following Eq.
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 Clearance = Rate of elimination / Plasma drug concn -----Eq. 15
Or

Cl = (dX/dt)/C -----Eq. 16

• Clearance is defined as the theoretical volume of body fluid

containing drug from which the drug is completely removed in a
given period of time.

• It is expressed in ml/min or litres/hour.

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Total Body Clearance:

• Elimination of a drug the body involves processes occuring in

kidney, liver, lungs & other eliminating organs.

• Clearance at an individual organ level is called as organ clearance.

• It can be estimated by dividing the rate of elimination by each organ

with the concentration of drug presented to it. Thus,

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Renal Clearance (ClR) = Rate of elimination by kidney/C -----Eq. 17

Hepatic Clearance (ClH) = Rate of elimination by liver/C ----- Eq. 18

Other organ Clearance (Clothers) = Rate of elimination by other organs/C

-----Eq. 19

• The total body clearance, ClT, also called as Total Systemic

Clearance, is an additive property of individual organ clearances.

• Hence, Total Systemic Clearance, ClT = ClR + ClH + Clothers -----Eq.

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• Because of the additive of clearance, the relative contribution by
any organ in eliminating a drug can be easily calculated.

• Clearance by all organs other than kidney is sometimes known as

non renal clearance (ClNR).

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