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Lab 1 - Mathematical Calculations

The document covers mathematical calculations and graphing techniques used in pharmacokinetics, focusing on the relationship between drug concentration and time. It explains the concepts of zero-order and first-order kinetics, linear regression, and the use of semi-log paper for data representation. Additionally, it includes examples of data analysis, rate constants, half-lives, and mathematical functions relevant to pharmacokinetic modeling.

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0% found this document useful (0 votes)
18 views32 pages

Lab 1 - Mathematical Calculations

The document covers mathematical calculations and graphing techniques used in pharmacokinetics, focusing on the relationship between drug concentration and time. It explains the concepts of zero-order and first-order kinetics, linear regression, and the use of semi-log paper for data representation. Additionally, it includes examples of data analysis, rate constants, half-lives, and mathematical functions relevant to pharmacokinetic modeling.

Uploaded by

arefyoussef408
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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(Lab 1)

Mathematical calculations
and use of semi log paper
 The language of science is mathematics and graphs are its
pictures.
 The “Y” variable, known as the dependent variable, is depicted
on the vertical axis (ordinate); and the
“X” variable, known as the independent variable, is depicted on
the horizontal axis (abscissa).
 It’s said that the “Y” varies with respect to “X” and NOT “X” varies
with “Y”
Y

For Example: if we will draw relation


between conc. of drug in plasma and time,
we will put time in “X” axis & conc. In “Y” axis,
because time is independent variable while
conc. of drug in plasma in dependent.
X
Straight line graphs:

 A graph is a straight line (linear) only if the equation from


which it is derived has the form:

Y = b ± aX , where:

y= dependent variable. Y

x= independent variable. Intercept

∆𝒀
m= slope of the straight line = Slope = -2
∆𝑿

b= the y intercept ( when x = 0 )


X

 Intercept means: value of Y when X equal Zero e.g. Y = -2X + 12


Linear regression
(Best fitting line)

Slope = +ve
Intercept

X
 An expression relating the plasma concentration
of drug (Cp) versus time (t)

Cp = Cpo.e-kt

 This relationship put in linear equation by taking ln


of both sides yield.

𝐥𝐧 𝑪𝒑 = 𝐥𝐧 𝑪𝒑𝒐 − 𝑲𝒕

Which the form y=b-ax “Linear”


 By drawing in Cartesian paper:
➢ If straight line → zero order.
➢ If Not straight → maybe 1st order → Draw in semi log
paper, if straight line → 1st order.

E.g.: When drawing relation between conc. of drug in


plasma and time following I.V injection
Cp
Cp

Semilog Paper
Cartesian Paper

So → 1st order
t t
Remember that:
Zero order First order
Rate Rate is constant independent on conc Rate α conc of reactant
-dc/dt=k -dc/dt=k concA
T1/2 CO / 2K 0.693/k
Dependent on initial conc (directly) Independent on initial conc
Graph on
Cartesian paper

slope = -k/2.303
slope= -k or we can use semilog paper to
obtain straight line without
taking log concentrations.
A) Show if these data follow zero order or first order
kinetics? Comment?
Time Conc
(hr) (mg/ml)
0 12
1 10
2 8
3 6
4 4
5 2
The concentration of drug C in plasma decreases a constant rate of 2 mg/ml for each
1 hour of time. Since the rate of change of concentration with respect to time is
constant; it is zero order kinetics
𝒅𝒄 𝟐𝒎𝒈
Rate of change of c with respect to time = /𝒉𝒓
𝒅𝒕 𝒎𝒍

Equation is ct= 12-2t


Semilog Paper

Don`t have zero on its Y axis. It is simply graph paper which has one
linear axis and one log axis. It is used in the case where the data range on
one axis is extremely large and/or does not follow a linear progression
B) Plot the following data on both semilog graph paper
and Cartesian paper

Time Conc
(hr) (mg/ml)
10 96
20 89
40 73
60 57
90 34
120 10
130 2.5
a) Does the decrease in the concentration of the drug in plasma
appear to be a zero order or first order process?

Since it is straight line on cartesian paper, so it is zero order


kinetics
b) What is the rate constant K?
k can be determined from slope of the curve
𝐶1 −𝐶2 96−73
Slope (–k)= → −𝑘 = → 𝐾 = 0.77 mg/ml/hr
𝑡1 −𝑡2 10−40

c) What is the half life?

𝑪𝟎 𝟏𝟎𝟒
𝒕𝟏 = = = 𝟔𝟕. 𝟑𝟑 𝒉𝒓𝒔
𝟐
𝟐𝒌 𝟐×𝟎.𝟕𝟕
d) What is the (AUC)130 0?

(𝐶0 + 𝐶13 ) (104 + 2.5) 𝑚𝑔


𝐴𝑈𝐶0130 = 𝑡130−0 = 130 − 0 = 6922.5 . ℎ𝑟
2 2 𝑚𝑙

e) Does the concentration of the drug extrapolate to zero on x-axis?


Yes because it is zero order kinetics
The area between time intervals is the area of a trapezoid
and can be calculated with the following formula :
When t is time and Cp1 in conc. Of drug in plasma at
1st time & Cp2 is conc. At other time.

𝟏𝟓−𝟏𝟎
[AUC]𝟒𝟑 = 𝟒 − 𝟑 = 𝟏𝟐. 𝟓 𝑿 𝟏 = 𝟏𝟐. 𝟓
𝟐

𝐶𝑝𝑛
[AUC]∞
0
= σ 𝑡𝑛
[𝐴𝑈𝐶] 𝑡𝑛−1 +
𝐾

 K = elimination rate constant obtained from the


slope of the terminal portion of the curve.
Mathematical concept
Pharmacokinetic models must be :

1) Simulative to the original data in the 1ry system.


2) Predictive

You must know that all designed in mathematical base so we must


know certain rules.
1. Expressing large and small numbers

AEn → A×10n
31600=3.16×104
0.00605=6.05×10-3
2.28E4=2.28×104

Functions:
Y=F(x) → mean that y is a changing parameters with respect to
x conc (dependant) with time (independent).
a) Exponential function :

If N = bx x → exponent b → base N → the


number when b is raised to the xth power 100 =102

Laws of Exponents

1. An Am = An+m
2. An/Am = An-m
3. A-n =1/An
4. (An)m = Anm
5. n√A = A 1/n
6. A0 =1 why?? A2/A2 = A2-2 = A0=1
b) Logarithmic Function :
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 If N = bx log bN= x

E.g. 16=42 → log 416 = 2

Basic logarithm
when the base equal 10 it is usually not written

log 1000= 3 log 101000= 3


c) Natural logarithm

instead using 10 as a base for logarithm a


natural logarithm (e) is used e= 2.718
If A= en → logeA=n → ln A=n

ln N= 2.303 log N

Ex : Ln 100 = 4.6 ???


[log 100 * 2.303] = 2*2.303 = 4.6
Laws of logarithms :
➢Log (nm) = log (n) + log (m)
➢Log [n/m]= log[n]-log[m]
➢Ln[1]=log[1]= zero
➢Log 0 : undefined
➢Log1/m= log 1- log m= zero – log m = -log m
➢Log m 2 = log m + log m = 2 log m
➢Log m -2 = -2 log m = 2 log 1/m

➢Log (ⁿ√m) = log m 1/n =1/n log m

➢Log m m =1

➢Ln e= log ee = 1 as ln=log e

➢Ln e=1 → ln e 1 = 1

➢Ln e –x = - x ln e = - x

➢Ln e5=5
1) Find the value of the following

a) Log 2.303 = 0.3622


3
b) In = In 3 - In 6.7 = - 0.80349
6.7

c) 2.3.e-1.1×3.2 = -0.06807

d) 2.6 ×
3 7
2.6 = (2.6)10 = 14116.709
2) Cp = Cpo *e-k.t find the value of k in the following expression
25= 50.e-4k (t= 4hrs)

−4𝑘 25
𝑒 = = e-4k = 0.5 Take In for the equation
50

In 0.5= In e-4k → In0.5 = -4k In e → In 0.5 = -4k

𝑰𝒏 𝟎. 𝟓
𝑲= = 𝟎. 𝟏𝟕𝟑𝟐𝟖
−𝟒
(3) How many half-lives would it take for 99.9% of any initial
concentration of a drug to decompose? Assume first order kinetics.
𝐾. 𝑡
log 𝐶 = log 𝐶 0 −
2.33

99.9 % decompose So 0.1 % remaining


0
𝐾. 𝑡99.9%
0
log 0.1% 𝐶 = log 100%𝐶 −
2.33
𝑲. 𝒕𝟗𝟗.𝟗% 𝟏𝟎𝟎%𝑪𝟎 𝑲. 𝒕𝟗𝟗.𝟗%
= 𝒍𝒐𝒈 𝟎
⟹ = 𝐥𝐨𝐠 𝟏𝟎𝟎𝟎 ⇒ 𝒕𝟗𝟗.𝟗%
𝟐. 𝟑𝟎𝟑 𝟎. 𝟏%𝑪 𝟐. 𝟑𝟎𝟑
𝟔. 𝟗𝟎𝟗 𝟎. 𝟔𝟗𝟑
= 𝒃𝒖𝒕 𝒕𝟏 =
𝑲 𝟐 𝒌

6.909
𝑡99.9% 𝑘
= ⇒ 𝑡99.9% = 9.69. 𝑡1 ⇒ 𝑡99.9% = 10. 𝑡1
𝑡1 0.693 2 2
2 𝐾
6) Mark (T) for true statements and (F) for false ones:
a) t1/2 is directly proportional to concentration in first order kinetics
b) In e-X= -X
c) 2.303 log X= In X
d) 726000 equals 7.26 × 106

e) so X= 39.81
𝑿
log( ) = 1.6 log X –log 3= 1.6  log x= 1.6 + log 3  log X= 2.077  X= 119.432
𝟑

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