Problem Set #2
1) List 5 factors that can influence the dissolution rate of a solid drug particle.
2) Compare transmembrane-limited absorption and dissolution rate-limited
absorption.
3) Estimate Vd for a drug when the volume of plasma and tissue are 5 and 30 L,
respectively and the fraction of drug bound in plasma is 0.3 and that bound in
tissue is 0.2.
4) “Loferin”, an antidepressant, was given as a 500 mg iv bolus to J. T., a 15 yr
old, 50 kg patient. Upon analyzing the plasma concentration profile, a half-life
of 10 hrs was determined for “loferin”. When the same dose was given as a
tablet to this patient, an AUC of 100 µg hr/ml was calculated. Determine the
absolute bioavailability for “loferin” in this patient. Assume a Vd of 0.5 L/kg
and one-compartment first-order elimination for “loferin”.
5) Compared to oral route of administration, what are the advantages and
disadvantages of the pulmonary route?
6) Circle the correct statement:
T F For rapidly dissolving drug particles, small differences in the rates
of dissolution affect the plasma concentration profile when intestinal
permeability is the rate limiting step.
T F A concentration gradient is essential for facilitated transport.
T F Nitroglycerin can be administered sublingually, transdermally or
orally.
T F The extent of plasma protein binding of a drug affects how much of
the drug is able to diffuse into tissues.
7) Use the table shown below to answer the following questions:
a) Give the correct order of dissolution rate in the small intestines for drugs A,
B, C and D. Assume a pH of 8.0 in the small intestines.
b) Give the correct order of diffusion rate through GIT membranes for drugs
A, B, C and D. Assume all drugs are in solution.
ABC D
pKa Weak acid
pKa 5.4
Quaternary
amine
Weak base
pKa 10
Neutral
Partition coefficient 5 1 10 50
