Introduction
1. Explain
Biopharmaceutics
Absorption
1. Define
absorption. Highlight phases of drug transfer from gastrointestinal absorption
site to systemic circulation.
2. Describe
the factors which may affect the oral absorption of drug process
3. Explain
the various mechanism of drug absorption from GIT with suitable example.
4. Write
about any six physiochemical factors that influence gastro - intestinal
absorption of drugs. Explain Biopharmaceutics Classification System of drugs
with examples.
5. State
the PH-partition hypothesis briefly. Based on the hypothesis, predict the
degree of
ionization of very weak, weak and strong
acidic and basic drugs from stomach and intestine.
6. Write
short notes on:
a. Rate
determining step
b. Area
under the curve (AUC) and its significance
Distribution
1. Explain
the physiological barriers that affect drug distribution. Discuss the various
patterns of drug distribution.
2. Why
is distribution of drugs not uniform throughout the body? Name the specialized
barriers to distribution of drugs. Explain any two of them.
3.
4. Highlight
the steps involved in drug distribution with a schematic diagram. Classify
various body tissues on the basis of perfusion rate. How age, obesity, diet,
diseases stats and drug interactions affect distribution of a drug? Explain
with examples.
1. Write
short notes on:
a. Volume
of distribution
Protein
binding
2. Write
the significance of protein drug binding.
2. Mention
the different body components to which drugs normally bind. Why is human serum albumin
considered a versatile protein for drug binding?
1. Write
short notes on:
b) Significance of plasma/tissue binding of drugs
Metabolism
1. Explain
metabolic pathways of drugs
2. Classify
the chemical pathway of drug metabolism with an example of one drug.
3. Define
first pass effect. Explain the primary systems which affect presystemic
metabolism of a drug.
1. Write
short notes on:
a. Enterohepatic
cycling of a drug with figure
b. Biotransformation
c. Consequences
of drug metabolism
Excretion
1. Discuss the combined effect of urine pH, drug
pka and lipid solubility on urinary excretion of drugs.
2. Explain
the parameter renal clearance and its relationship with excretion by kidney
3. List
the factors that affect clearance of drug.
4. Define
drug excretion. Describe the mechanism of renal drug excretion. How does drug
PK, and urine pH affect renal drug excretion? Explain briefly with suitable
examples.
1. Write
short notes on:
a. Half-life b. Elimination rate
constant c. Hepatic clearances
d. Intrinsic
clearance e. Renal clearance f. Clearance
g. Renal excretion
of drug
Bioavailability
1. Define
bioavailability and bioequivalence. What are the objectives of conducting
bioequivalence studies? Design a protocol for conduction of Bioequivalence
studies.
2. What
are the differences between cross -over and parallel study designs in
bioequivalence studies?
3. Difference
between, Bioavailability and bioequivalence
4. Briefly
explain the various approaches to enhance the bioavailability of the drug from
suspension dosage form.
5. Describe
the various approaches to enhance the bioavailability of BCS class II drug.
1. Define
pharmaceutical equivalent, pharmaceutical alternative, therapeutic equivalence
and bioequivalent drug products. Write about indirect methods of measurement of
Bioavailability.
2. Write
down the clinical significance of bio equivalence.
3. Describe the factors that affect the
bioavailability of orally -administered drugs.
4. Describe
the pharmaceutics methods of assessing bioavailability.
1.
Non linear pharmacokinetics
1. Write
short notes on:
a. Non-linear
pharmacokinetics
2. Differentiate
between linear and nonlinear kinetics. Discuss the causes of nonlinearity
inpharmacokinetics with examples
Compartmental
kinetics
Write short notes on:
Loading
and maintenance dose
1. What
is the significance of analysis of urine data? Explain cumulative frequency
versus time and ARE. versus time plots.
2. What
are the advantages of using urine data over plasma data for determining Ke.
What are the different criteria to obtain a valid urine data? Describe the
different methods of determining Ke from urinary excretion data.
1. How
will you determine pharmacokinetic parameters model independently?
2. Describe
how would you calculate the AUC after oral administration of drug.
3. Describe
the characteristics of open one and two compartment models of administration.
Draw the model schemes, Label it and write the differences of these models.
4. Differentiate
between the characteristics of zero order and first order kinetics with
suitable examples and graphical
representations. Mention the assumptions of single compartment open mode with a
diagram.
5. Define
pharmacokinetic models. How would you describe a one compartment open model for
extravascular administration? Explain schematically and graphically along with
various assumptions to describe the model.
6. Describe
the various parameter of plasma concentration time profile obtain after a
single dose of a drug administered by extra vascular route.
1. Explain
the differences between:
a) ARA method and ARE
method
2.
3.
Clinical application:
1. Write
down applications of pharmacokinetic principle. How can you adjust dosage
regimen for a renal failure patient?
2.
3. Write
short notes on:
a. Dosage
regimen design in renal failure
b.
Numericals:
1. Use
model independent method to calculate AUC, AUMC and MRT of a drug with the
following plasma concentration profile after intravenous bolus injection of
50mg of the drug:
Time (hr) 0 0.5 1 2 4 6 8 12
Con (mg/ml) 4 3.1 2.5 2 1.2 0.8 0.5 0.3
2. Given
fu of ibuprofen to albumin is 0.005. Calculate fu of albumin concentration
decreases from 43 g/L to 28 g/L.
3. The
normal dose of a drug is 500 mg. If the fraction excreted unchanged in urine is
0.60. Calculate the dose for a patient whose creatinine clearance is reduced to
26 ml/min? Calculate the new dosing interval if the normal dosing frequency is
every 8 hours.
4. After
an administration of 300 mg of drug, blood samples were taken at various time
intervals and the following plasma concentration vs time profile was observed.
Time (hr) 0.5 1 1.5 2 3 5 7 9
Conc (mcg/ml) 23 29 28 26 19 10 5.5 3
Assuming that the drug is
completely absorbed and using method of residual, calculate:
a) Elimination rate
constant b)
Elimination half-life
c) Absorption rate
constant d)
Absorption half-life
e) Volume of
distribution f) Peak time
g) Peak Plasma
Concentration h)
Total area under the curve
5. Phenytoin
was administered to a patient at dosing rates of 150 and 300 mg/d,
respectively. The steady - state plasma drug concentrations were 8.6 and 25.1
mg/L, respectively. Find the Km, and Vmax of this patient. What dose is needed
to achieve a steady-state concentration of 11.3 mg/L?
6. 200
mg of a drug was administered as IV bolus injection and 20% of dose had been
obtained as an unchanged drug in urine after 10 hours. The total recovery of
unchanged drug in urine after infinite time was 100 mg. Calculate the half -
life of the drug.
4. A
patient was infused for 6 hours with a drug (Ke = 0.01 h'; V4 = 10 L) at a
ratee of 2 mg/h. What is the concentration of the drug in the body 2 hours
after cessation of the infusion?
5. Gentamicin
has an average elimination half = life of approximately 2 hours and an apparent
volume of distribution of 20% of body weight. It is necessary to give
gentamicin, 1 mg/kg every 8 hours by multiple IV injections. To a 50 kg woman
with normal renal function. Calculate:
a) Cssmax b) Cssmin c) Cssav,,
when steady state is achieved.
6. An industrial pharmacist would like to design
a sustained release drug product to be given 12 hourly. The drug has an
apparent Vd of 15L, and elimination half-life of 3.5hrs and desired therapeutic
plasma drug concentration of 25mg/l, calculate the zero-release rate of the
product and total amount of drug needed, assuming no loading dose is needed.
7. A drug has elimination rate constant of
0.173hr-1. The drug initial concentration when given by IV Bolus
administration is 8.4 mg/ml. find out the time required for the drug to get
reduced to 99.9% of its initial concentration. What is its t1/2.
8. After the oral administration of 300mg of drug
X, the following plasma concentration are observed. Assuming the drug is 75%
absorbed
~Time
(hrs) 025 05 075
1 2 3 4
6 9 12
Con(mg/l) 2.28 4.33 5.67 8.81 9.31 9.68 10.25 7.51 4.98 3.25
Calculate
elimination half-life, absorption rate constant (Ka,), the vd, peak time(tmax)
and plasma concentration (Cmax).
9. The apparent volume of distribution of
fluoxetine is 30001. calculate
i)
the amount of drug in the body when the plasma concentration is 1ng/ml.
ii)
the plasma concentration when the amount of drug in the body is 2mg,
iii}
the percentage of drug that is present in plasma.
10. a)
Estimate the creatinine clearance of a 30-year-old, 70kg man with serum
creatinine value 2.0%. What is the renal function value of such a patient?
11. b)
A drug with an elimination half-life of 1 hour was given to a male patient
(80kg) by intravenous infusion at a rate of 300mg/hr. A 7 hours after infusion,
the plasma drug concentration was 11 mcg/ml.
i)
What is the total body clearance for this
drug?
ii)
What is the apparent Vd for this drug
assuming a one-compartment model?
iii)
If the drug is not metabolized and is
eliminated only by renal excretion, what is the renal clearance of this drug?
iv)
What would then be the probable mechanism
for renal clearance for this drug?
12. a) Concentration of Amoxicillin in plasma is
2mg/ml and 5mg/ml at 6 and 4 hours respectively. Calculate plasma half-life(t1/2)
and elimination rate constant (Ke).
b) Half-life of a drug in
a patient receiving IV bolus is 6 hours. If Vd is 30L, calculate the steady state
plasma concentration for a continuous IV infusion of 40mg/hr.
13. A
new antibiotic drug was given a single intravenous bolus of 4mg/kg to a
35-year-old healthy male adult (body weight 75kg). The pharmacokinetics of the
plasma drug *concentration-time curve for this drug fits a one-compartment
model. The equation of the
curve that best fits the
data is Ct=78e-0.46t. Determine the following (assume units of mcg/ml
for Ct and hr for time);
i) What is the t1/2?
i) What is the Vd?
iii) What is the plasma
level of the drug after 4hours?
iv) How much drug is left
in the body after 4 hours?
v)
Assuming the drug is no longer effective
when levels decline to less than 2mcg/mg, when should you administer the next
dose?
14. An
IV. bolus dose of 325mg of a drug was administered to a healthy volunteer and
the following plasma drug concentration data was obtained:
- Time 2 4 6
8 10 12 16 20
- PDC (mcg/ml) 18.5 10.1
5.8 3.3
1.8 1.0
0.31 0.21
Calculate:
a) Elimination half-life b) Apparent volume of distribution
c)Total systemic
clearance d) AUC
15. The equation that
best fits the pharmacokinetics of Paracetamol after oral administration of pcm
500mg dose is: C =1.18 (e-0.24t – e-1.6t). Assuming one
compartment kinetics and units of C (mcg/ml) and that of t is hrs. Calculate
a. Elimination
half-life b. Cmax c. Tmax d) Apparent VD if f is 1
15. a)
A 70 kg volunteer is given an intravenous dose of an antibiotic and serum
contraction was determined at 2 and 5 hrs after administration. The
concentrations were 1, 2 and 0.3 mcg/ml respectively. What is the biologic half
— life for the drug assuming to first order elimination kinetics?
b) A product degrades
according to first order kinetics. At the time of preparation, the concentration
of active ingredient was 23 mcg, and after five months the concentration of active
ingredient reduced to 21 mcg. Calculate the time when the concentration of
active ingredient in the product will be 17.5 mcg Ans: 15.02 months
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