1.

Hemodialyzer clearance
One major goal of hemodialysis is to remove urea among other wastes. Blood urea
concentration before and after hemodialysis over time T are referred as co and cT,
respectively. The blood urea concentration is measured by blood urea nitrogen (BUN) assay.
The urea reduction ratio (URR) is defined as cT/co.
Let’s consider a single compartment model, in which urea enter from blood to dialysate as a
first order reaction with reaction constant k1.
%!
𝑐!"##$ (𝑡) → 𝑐$&'"()'*+ (𝑡)
1) Derive an expression for cT/co using this model.
2) Define urea clearance 𝐾 = 𝑘, 𝑉, where V is the total blood volume of the patient. Derive
an equation to measure K.
3) For a BNU measurement curve below, assuming the patient blood volume V is 5 liter,
calculate urea clearance K.

2. Drug eluting stent

Under certain assumptions, the release of a drug in the polymer coating of a drug eluting
stent can be calculated using the Higuchi equation:
𝑀*
= ,𝑐) (2𝑐&-& − 𝑐) )𝐷𝑡 (1)
𝐴
where D is the diffusivity of the drug in the polymer (cm2/day), Cini is the amount of drug
dispersed per unit volume in the polymer coating (g/cm3), Cs the solubility of the drug in the
polymer (g/cm3).
 a. What are the assumptions that Higuchi equation is valid? Do you think drug eluting
stent meet these assumptions?
b. Let’s say this equation can be used, determine 24 hour of drug release if drug eluting
stent is modeled as a cylinder of 1 mm in diameter, 10 cm long, D = 0.01 cm2/day, Cini is
0.2 g/cm3, Cs is 0.001 g/cm3.
c. In the classical derivation of the Higuchi equation, a pseudo-steady-state approach was
used to draw the conclusion that the drug concentration–distance-profile between the
surface of the film and the “diffusion front” is linear. The pseudo-steady-state is valid for
the ointment/polymer containing initially a large excess of drug compared with the drug
solubility and the dissolution is much faster than the diffusion. Use Fick’s second law to
make an argument for the linear drug concentration–distance-profile.
3. Permeability measurement for lung/intestine on chip
Permeability is important for biological organs such as lung and gastrointestinal tract. A
simple model of such tissue is a layer of epithelial cells grown on a porous membrane. Let’s
consider how permeability can be measured in such case using a Transwell device, in which
a porous membrane separates two chambers: the apical chamber and the basolateral
chamber. In the illustration below, two Transwell devices are shown. The left one has only
the porous membrane, without cells. The right one has a confluent layer of epithelial cells
grown on the porous membrane. We can consider the barrier (porous membrane or porous
membrane plus epithelium) as a chemically homogeneous slab.

To measure the permeability in the apical-to-basolateral direction, fluorescent molecule

(e.g. FITC-Dextran 4 kDa) is added to the apical compartment of the epithelial barrier. Very
small amount of samples from the basolateral can be taken periodically to measure the
fluorescence molecule concentration.
The apparent permeability coefficient 𝑃 (𝑚 ∙ 𝑠 ., ) can be defined as:
𝐾𝐷
𝑃= (2)
ℎ
where 𝐾 is the distribution coefficient between the medium
in the barrier and the apical and basolateral chamber
solutions as in illustration on the right (same concept in Lab 2
and you can assume linear concentration distribution of the
fluorescent molecule in the barrier as shown), 𝐷 is the
diffusivity of the fluorescent molecular in the barrier, and ℎ is
the thickness of the barrier.
(1) Under the sink conditions, i.e. the fluorescence molecule concentration in the
basolateral chamber can be ignored compared with the molecular concentration in the
apical chamber and the later stays the same as its initial concentration, show that 𝑃 can
be measured using the equation below:
1 𝑑𝑀
𝑃= (3)
𝐴𝐶' 𝑑𝑡
where 𝑀 (𝑚𝑜𝑙) is the fluorescent material being transported in the basolateral
chamber, 𝑑𝑀/𝑑𝑡 (𝑚𝑜𝑙 ∙ 𝑠 ., ) is the steady-state transport rate, 𝐴 (𝑚/ ) is the surface
area of the membrane, and 𝐶' (𝑚𝑜𝑙 ∙ 𝑚.0 ) is the initial concentration of fluorescent
molecule added to the apical compartment. (Hint: use flux definition and Fick’s first law
in the barrier.)
(2) Under the more general situation, we consider the fluorescent molecule concentration
in the apical and basolateral chambers are both time-dependent. If the solution volumes
in apical chamber and basolateral chamber are 𝑉' and 𝑉! , respectively, the total amount
of the fluorescent molecule (account for both chambers) is 𝑀* , and the initial
concentration (at 𝑡 = 0) of the fluorescent molecule in the basolateral chamber is 𝐶!,# ,
derive the time dependent fluorescent molecule concentration in the basolateral
chamber 𝐶! (𝑡), which normally can be measured:
𝑀* 2 32 𝑀*
. " # 45*
𝐶! (𝑡) = >𝐶!,# − @ 𝑒 2" 2# + (4)
𝑉' + 𝑉! 𝑉' + 𝑉!
Hint: (a) Use mass balance of the fluorescent molecule; (b) relates fluorescent molecule
flux in the basolateral chamber to its flux in the barrier; (c) the flux in the barrier can be
derived using flux definition and Fick’s first law as in part (1)
(3) To measure the permeability of the confluent cell layer 𝑃6 , you measure the
permeability of the membrane only 𝑃7 in the left chamber of the illustration and the
permeability of the membrane plus confluent cell layer 𝑃* in the right chamber of the
illustration. Prove 𝑃6 can be calculated as below:
𝑃* 𝑃7
𝑃6 = (5)
𝑃7 − 𝑃*
(Hint: use resistors in series and the fact that permeability is the inverse proportional to
resistance.)