Lab 4

Course Name

Biopharmaceutics and Pharmacokinetics

CPT3206

Lab 4

I- Pharmacokinetics of drugs administered by

intravenous route

Calculation of drug elimination rate constant from urinary excretion data

 Lab 4

Variables calculated From urine data

1-Cumulative amount excreted in urine in a time interval (Du )

2-Total amount excreted in urine (Du∞)

3-Amount remaining to be excreted in urine (Du∞ - Du )

4-Excretion rate in urine (dDu / dt ) or (∆ Du / ∆t )

 Lab 4
2- Calculation of drug elimination rate constant from urinary excretion data

I. Rate Method
By plotting rate of urinary excretion dDu/dt versus time (t*)
 Lab 4

Time interval (t) Amount in urine Du/dt Midpoint (T*)

0-2 500 500/2-0 2+0/2
2-4 300 300/4-2 2+4/2

Log dDu/dt

T*
 Lab 4

II. Sigma Minus Method

By plotting Log ARE ( Amount remained to be excreted) , (Du∞ - Du )
versus time

Kt
Equation: Log Du∞ - Du = log Du ∞ -
2.303
Log Du∞ - Du
Du∞

Slope = - K /2.303

T
 Lab 4

*Total clearance (𝑪𝒍𝒕 ):

𝑪𝒍𝒕 = 𝑲𝑽𝑫
𝑪𝒍𝒕 = 𝑪𝒍𝒓 + 𝑪𝒍𝒏𝒓

*Renal clearance (CLr):

𝑪𝒍𝒓 = 𝒌𝒆 𝑽𝑫

*Non-renal clearance (𝑪𝒍𝒏𝒓 ):

𝑪𝒍𝒏𝒓 = 𝒌𝒎 𝑽𝑫

*Fraction of drug excreted unchanged (Fu):

Du∞ Ke
Fu = 𝑭𝑫𝟎 =
K
 Lab 4

Problems
 Lab 4

I) A single I.V dose of a new antibiotic was given to a 50 Kg woman

at a dose level of 20 mg/Kg. urine and blood samples were removed
periodically and examined for parent drug. The data is tabulated in
following table:
Time (hr) Cp (mcg/ml) Du (mg)
0.25 4.2 160
0.50 3.5 140
1.00 2.5 200
2.00 1.25 250
4.00 0.31 188
6.00 0.08 46

Estimate (K) by three methods “Plasma – rate method – Sigma minus

method
 Lab 4

II) A bolus IV dose of 700 mg of tetracycline HCl was given to an adult male and
over 2 hours-time intervals, urine was collected and assayed for drug. Assuming
first order kinetics and given the data shown in the Table below, plot dDu/dt
versus midpoint time given that average volume distribution is 10 L

Plot the data on semi log paper Amount of drug excreted

Time (hr)
in urine
Evaluate:
i. Total body clearance 0-2 400
ii. Renal clearance 2-4 126
iii. Non renal clearance 4-6 40
6-8 12.6
III) Sulfaethyl thiadiqzole was injected i.v. in a dose of 2 g to a male
weighing 80 kg . The amount of drug excreted unchanged in the
urine is shown in the following table .
Time interval 0-6 3-6 6-9 9-12 12-15 15-24 24-48

Amount 534 436 181 139 110 202 195

excreted (mg)

A. Determine the t1/2 from the urine data using excretion Rate method
& estimate the fraction excreted unchanged .
B. Determine the t 1/2 from the urine data using the cumulative
excretion method .