Adamson University

College of Pharmacy

Biopharmaceutics and
Pharmacokinetics
Prepared by:
Darwin L. Obel, RPh, MSPharm
April Mergelle R. Lapuz, RPh
 Adamson University
College of Pharmacy

Mathematical Fundamentals

of Pharmacokinetics
Prepared by:
Darwin L. Obel, RPh, MSPharm
April Mergelle R. Lapuz, RPh
Objectives:

At the end of the topic, students must be able to:

• Perform basic mathematical operations that are important in doing
pharmacokinetic calculations.
• Discuss and differentiate the different Pharmacokinetic models.
• Explain using examples why drugs follow one-compartment, two-
compartment, or three-compartment kinetics.
Laws of Exponents

Law Example
x1 = x 61 = 6
x0 = 1 70 = 1
x-1 = 1/x 4-1 = ¼
xmxn = xm+n x2x3 = x2+3 = x5
xm/xn = xm-n x4/x2 = x4-2 = x2
(xm)n = xmn (x2)3 = x2×3 = x6
(xy)n = xnyn (xy)3 = x3y3
(x/y)n = xn/yn (x/y)2 = x2 / y2
x-n = 1/xn x-3 = 1/x3
Laws of Logarithm

• log ab = log a + log b

• log a/b = log a – log b
• log ax = x log a
• -log a/b = log b/a
• ln e-x = -x
Logarithm
• the logarithm of a positive number N to a given base b is the exponent x to which the base must
be raised to equal the number
N= bx
• Therefore:
Logb N = X

• Common logarithm = base of 10

• Ex: 100 = 102
• Log 100 = 2
• 100 = antilogarithm of 2

• Natural logarithms (ln) use the base e, whose value is 2.718282. To relate natural logarithms to
common logarithms, the following equation is used:

• 2.303 log N = ln N
Sample Problems

1. Find the log of 35.

2. Find the log of 0.028.
3. Find the antilog of 0.028.
4. Evaluate e-1.3.
Sample Problems

5. Find the value of k: 25=50e-4k

Sample Problems

6. Evaluate the expression: using t = 2; Cp0 = 35; k=0.15

• Find C: C = Cp0e-kt
!.#$# &!
• Find C: 𝑘 = 𝑙𝑜𝑔
% &
Units in Pharmacokinetics
Rates and Order of Reaction

Rate
• The rate of a chemical reaction of process is the velocity with which
the reaction occurs

Half-Life
• Half-life (t 1/2) expresses the period of time required for the amount
or concentration of a drug to decrease by one-half
Zero Order Reactions

• The amount of drug is decreasing at a constant time interval

• Amount of drug eliminated per time interval is constant
• Fraction eliminated per time interval is not constant

𝐶 = −𝑘! 𝑡 + 𝐶!
Where
C0 = drug concentration at time = 0
C = drug concentration at time t
K0 = zero order elimination rate constant

0.5𝐶!
𝑡"/$ =
𝑘!
Sample Problem

• Calculate the zero-order rate constant ([ng/mL]/min) if the initial

concentration of the drug is 200 ng/mL and that at t = 30 min. is 35
ng/mL.
• When does the concentration of drug equal to 100 ng/mL?
First Order Reactions

• The amount of drug is decreasing at a rate that is proportional to

the amount of drug remaining
• Amount of drug eliminated per time interval is not constant
• Fraction eliminated per time interval is constant

2.303 𝐶!
𝑘= 𝑙𝑜𝑔
𝑡 𝐶
Where
C0 = drug concentration at time = 0
C = drug concentration at time t
K = first order elimination rate constant
0.693
𝑡"/$ =
𝑘
Sample Problem

• Calculate the time needed for 70% of the drug to disappear. k =

0.04/hr.
• Calculate the t1/2.
Sample Problem
Plot the following data:
Time (minutes) Drug A (mg) • Does the decrease in the amount
10 96.0 of drug A appear to be a zero-
order or a first-order process?
20 89.0 • What is the rate constant k?
40 73.0 • What is the half-life t1/2?
60 57.0 • Does the amount of drug A
extrapolate to zero on the x-axis?
90 34.0
• What is the equation for the line
120 10.0 produced on the graph?
130 2.5
Sample Problem
Sample Problem
Plot the following data:
Time (minutes) Drug A (mg) • Does the decrease in the amount
4 70.0 of drug A appear to be a zero-
order or a first-order process?
10 58.0 • What is the rate constant k?
20 42.0 • What is the half-life t1/2?
30 31.0 • Does the amount of drug A
extrapolate to zero on the x-axis?
60 12.0
• What is the equation for the line
90 4.5 produced on the graph?
120 1.7
Sample Problem
Plotting Zero order data
Plotting First order data
Analysis of Plasma Concentration versus Time Data After IV Bolus
Administration
• https://www.boomer.org/c/p4/js/w030901/index.php

Calculate Parameter Values from Two Data Points from a Line drawn
through Data Collected after an IV Bolus
• https://www.boomer.org/c/p4/c04/c0414.php#js1

Calculate Cpt after an IV Bolus

• https://www.boomer.org/c/p4/c04/c0411.php#js1

Plot of Cp versus Time

• https://www.boomer.org/c/p4/js/w040501/index3.php
Pharmacokinetic Models
• Simulate the rate processes of drug absorption,
distribution, and elimination to describe and predict
drug concentrations in the body as a function of time.

• Hypothetical structures that are used to describe the

fate of a drug in a biological system following its
administration.
One-Compartment Model
• After drug administration, this
model assumes that the drug
achieves instantaneous
distribution throughout the body
and the drug equilibrates
instantaneously between tissues
Two-Compartment Model
• Resolves the body into central and peripheral compartment
• Central compartment - tissues that are highly perfused – Heart,
lungs, kidneys, liver and the brain
• Peripheral compartment – less perfused – muscle, fat and skin
• The difference from one compartment model is that the drug does
not achieve instantaneous distribution.
Two-Compartment Model
Two-Compartment Model

FIGURE 5-1 Plasma level–time curve for the two-compartment open model (single IV dose) described in Fig. 5-2 (model A). (Source:
Applied Biopharmaceutics and Pharmacokinetics, 7e by Shargel and Yu)
Example

Identify if the following drugs follows one/two-compartment model

• Aminoglycosides (15-20mins distribution)
• Vancomycin (2-4 hours distribution)
• Digoxin (4-6 hours distribution)
END OF LECTURE!

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