Menoufia University Faculty of Pharmacy

Department Of Pharmaceutical Technology

Practical Exam for 3rd Level Pharmacy Students
Course Title: Biopharmaceutics and Pharmacokinetics
Date: Pages: 5 Total Marks: 20 Time allowed: 90 min

Student name: …………………………………… ID:…………………………

Answer the following questions and make sure to provide unit for each parameter:

1. You are provided with two drugs having the same functional group. Depending on their
partition coefficient data, which of them will be selected if the main target is to attain slow
drug release after being entrapped into lipidic nanoparticles? Why? (2.5 Marks)

Why?D1 since it is of
Drug 1 Cinitial= 5 g/L Co= 2.5 g/L Cw= 2.5 K1=1
higher Co, so Higher K so
higher lipidic NP
Drug 2 Cinitial= 4 g/L Cw= 3 g/L Co= 1 K2 = 0.3
partitioning

2. Alcohol elimination data is plotted using normal graph paper (2.5 Marks):
a) Calculate the rate constant of the elimination process.
b) Calculate the concentration of drug in the body 20 h after administration of initial dose.
c) What is the 2nd half-life of the drug immediately after administration?
• Intercept = Co= 120 ug/mL
130
• K= -Slope = - (25-120)/(8-0) = 11.88 h-1 120
110
• C= Co-Kt 100
Concentration μg/mL

90
= 120 – (11.88 * 20) = -117.6 ug/mL 80
The -ve sign means that the drug is 70
60
totally eliminated 50
40
• 2nd t1/2 = 0.75 C0/K 30
20
= 0.75*120/11.88= 7.58 h 10
0
0 1 2 3 4 5 6 7 8 9 10
Time (h)

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 3. A single IV bolus dose of 100 mg/Kg was administered to the patient of 60 kg body weight.
The Vd = 30 L. Plasma concentrations (mg/L) were plotted versus time using a semi-log
graph paper. Draw the line representing this profile and answer the following: (2.5
Marks)
a) Calculate half-life time t1/2. b) Calculate drug clearance (Cl) from the body.
c) Calculate the Y-intercept if the total dose is 3000 mg? d) Calculate area under curve.
e) What is the time required for the initial drug concentration to decrease to 2 mg/L.

• Intercept = Cp0 = 200 mg/L

• K = - Slope *2.303

= - (log 3 – log 200) / (16-0)

= - (0.48-2.3)/16= 1.82/16 = 0.114 h-1

a) t1/2= 0.693/K =0.693/0.114= 6.08 h

Concentration (mg/L)

b) Cl= K*Vd= 0.114 * 30= 3.42 L/h

c) Cp0 = D/Vd = 3000/30= 100 mg/L
d) AUC = Cp0/K= 200/0.114 = 1754.39 mg.h/L
= D/Cl= 6000/3.42= 1754.39 mg.h/L
e) log C= log Co – Kt/2.303
t = (log C0 -log C)*2.303/K
= (2.30 – 0.30)*2.303/0.114
= 2 *2.303/0.114 = 40.40 h

Time (h)

2
4. A drug was infused into a patient at 2 mg/h rate for 6 h. The K of the drug = 0.01 h–1 and
Vd= 10 L. (2.5 Mark)
a) What is the concentration of the drug in the body 2 h after cessation of the infusion?
b) How many half-lives required to reach 50% of Cpss?
c) What is the time required to achieve at least 20% of steady state?
• log C= log Co – Kt/2.303
• C0 = ?????
𝑲𝟎 𝟐
• Cp= 𝑲×𝑽𝒅 (1– e-Kt) = 𝟎.𝟎𝟏 ×𝟏𝟎 (1– e-0.01 * 6) = 20 * (1- 0.94)= 20*0.06= 1.2 mg/h
• log C= log Co – Kt/2.303
= log 1.2 - (0.01*2) / 2.303 = 0.08 - 0.0087= 0.0713 mg/L
• C = anti log 0.0713 = 1.19 mg/L
𝐥𝐧 (𝟏 −𝑭𝒔𝒔) 𝐥𝐧 (𝟏 −𝟎.𝟓) − 𝟎.𝟔𝟗𝟑∗𝒕𝟎.𝟓
• 1 t1/2 or t= – = – 𝟎.𝟔𝟗𝟑/𝒕𝟎.𝟓 = – = 1 t1/2
𝑲 𝟎.𝟔𝟗𝟑
𝐥𝐧 (𝟏 −𝑭𝒔𝒔) 𝐥𝐧 (𝟏 −𝟎.𝟐) − 𝟎.𝟐𝟐𝟑
• T0.2 = – 𝑲
=– 𝟎.𝟎𝟏
=– 𝟎.𝟎𝟏
= 22.3 h

5. If an administered dose is 500 mg. The K= 0.7 h-1 and the drug shows 70% elimination
via renal excretion. The Clm = 1.8 L/h. (2.5 Mark)
a) Calculate Xu and Xm. b) Calculate TBC. c) Calculate Vd.

• Fe = 70/100= 0.7 ● Fm= 30/100= 0.3

• Xu = D * Fe= 500 * 0.7 = 350 mg ● Xm= D * Fm = 500 * 0.3= 150 mg
• Fm = Clm/TBC ● TBC = Clm / Fm = 1.8 / 0.3 = 6 L/h
• Vd = TBC/K = 6 / 0.7 = 8.57 L

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6. A patient received a single 100 mg oral dose of bronchodilator that is completely
absorbed after administration. The Ka = 0.771 h-1, Y-intercept of elimination phase = 75
g/L, K = 0.552 h-1, and tmax = 1.5 h. (2.5 Marks)
a) Calculate Cpmax. b) Calculate Vd. c) Calculate TBC. d) Calculate AUC.
e) Calculate tmax if the initial dose is increased into 10 mg oral dose.

𝑲𝒂∗𝑭∗𝑫
• D= 0.1 mg ● Ka= 0.771 h-1 ● Intercept == 𝑽𝒅 (𝑲𝒂−𝑲) = 75 mg/mL

• K= 0.552 h-1 ● tmax = 1.5 h

𝑲𝒂∗𝑭∗𝑫
• Cpmax = 𝑽𝒅 (𝑲𝒂−𝑲) [e-K*tmax – e-Ka*tmax]

= Intercept [e-K*t – e-Ka*t] = 154 [e-0.552 * 1.5 – e-0.771 * 1.5] = 75 [0.437 - 0.313]
= 75 * 0.142 = 9.3 mg/L

𝑲𝒂∗𝑭∗𝑫
• = 75
𝑽𝒅 (𝑲𝒂−𝑲)
𝑲𝒂∗𝑭∗𝑫 𝟎.𝟕𝟕𝟏 ∗𝟏∗𝟎.𝟏 𝟎.𝟎𝟕𝟕𝟏
• Vd = 𝟕𝟓 (𝑲𝒂−𝑲) = 𝟕𝟓 (𝟎.𝟕𝟕𝟏−𝟎.𝟓𝟓𝟐) = = 0.00469 L
𝟕𝟓 (𝟎.𝟐𝟏𝟗)

• TBC = K * Vd = 0.552 * 0.00469 = 0.00259 L/h

• AUC = F * D / TBC = 1* 0.1 /0.00259 = 38.61 mg.h/L
𝟐.𝟑𝟎𝟑 𝑲𝒂 𝟐.𝟑𝟎𝟑 𝟎.𝟕𝟕𝟏 𝟐.𝟑𝟎𝟑
• tmax = 𝑲𝒂−𝑲 log = 𝟎.𝟕𝟕𝟏−𝟎.𝟓𝟓𝟐 log 𝟎.𝟓𝟓𝟐 = 𝟎.𝟐𝟏𝟗 * log 1.4 = 10.52 * 0.146= 1.53 h
𝑲

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7. A patient administered an IV bolus before acquiring an acute renal disease. He continued
the course regimen after being diagnosed. The drug mainly shows renal excretion via 1st-
order process. The table below displays the parameters assayed before renal impairment
(values are not shown). Answer with increased ( ↑ ), decreased ( ↓ ), or the same ( = ) for
each parameter remeasured after developing renal diseases (2.5 Marks).
Before renal disease K t1/2 Vd TBC AUC
After renal disease ↓ ↑ = ↓ ↑

8. Mark each of the following sentence with “T” if it is true or “F” if it is false (2.5 Marks)
a) Plasma concentration-time profile of a drug is independent of the dosage form. F
b) In zero-order elimination, the change in drug concentration by time is variable. F
c) The concentration-time phases of a multiple-compartment model of drug elimination
T
from the body, are straight lines in the semi-log scale.
d) In IV bolus, Cp0 is dose dependent, while in IV infusion, Cpss is dose independent. T
e) A higher dose and less frequent administration are required to attain higher Cp and to
T
get the pharmacological effect, respectively, if the drug possess a large Vd.

Equations
• Partition coefficient: K= Co/Cw Cintial= Co+Cw
𝑌2−𝑌1
• Zero-order kinetics: C = C0 – K0t Slope= – K K (amount/time)= - Slope = - 𝑋2−𝑋1

Intercept= C0 1st t1/2= 0.5 C0/K 2nd t1/2= 0.75 C0/K tshelf life= 0.1 C0/K
log 𝑌2−log 𝑌1
• First-order kinetics: log C= log C0 – (Kt/2.303) Slope= – K/2.303 =
𝑋2−𝑋1

K (time-1) = - Slope * 2.303 Semi-log intercept= C0 t1/2= 0.693/K

tshelf life= 0.105/K
• IV bolus: Cp0= D/Vd TBC (volume/time)= K*Vd
AUC (amount . time /volume)= Cp0/K = D/TBC log C= log C0 – (Kt/2.303)
log 𝑌2−log 𝑌1
Slope= – K/2.303 = K (time-1) = - Slope * 2.303 Semi-log intercept= Cp0
𝑋2−𝑋1

t1/2= 0.693/K
𝐾𝑎∗𝐹∗𝐷 𝐾𝑎∗𝐹∗𝐷
• Oral DFs: Cp = 𝑉𝑑 (𝐾𝑎−𝐾) [e – K * t – e – Ka * t
] Semi-log intercept (Y intercept) = 𝑉𝑑 (𝐾𝑎−𝐾)
𝐾𝑎∗𝐹∗𝐷 2.303 𝐾𝑎
Cpmax= 𝑉𝑑 (𝐾𝑎−𝐾) [e – K * t max – e – Ka * t max] t or tmax = 𝐾𝑎−𝐾 log 𝐾
𝐹∗𝐷
F= Xplasma /D AUC(amount . time /volume)= 𝑇𝐵𝐶 TBC (volume/time)= K*Vd
𝐾0 𝐾0 𝐾0
• IV infusion: Cp= (1– e – Kt) Cpss= = Cp= Cpss (1– e – Kt)
𝐾×𝑉𝑑 𝐾×𝑉𝑑 𝑇𝐵𝐶
ln (1 −𝐹𝑠𝑠) ln (1 −𝐹𝑠𝑠)
TBC(volume/time)= K*Vd= K0 /Cpss t=– 𝐾
=– 0.693
× 𝑡1/2

• Elimination: D= Xu + Xm K=Ku+Km TBC(volume/time) =Clu+Clm = K * Vd

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Clu =Ku*Vd Clm =Km*Vd

Fe= Xu/D = Ku/K = Clu/TBC Fm= Xm/D = Km/K = Clm/TBC

* Best Wishes *