Cell Biology 6
- transport 1st
Sung Youn Lee, PhD. Student
Veterinary collage, Room 320
02 450 3719, 016 293 6059
leevet@paran.com
Clinical case
• Patient : Dog, greyhound, sprayed female,
11 years old
• Presenting signs and complaints :
escaped from a fence-in backyard and
was gone for 5 days; returned weak and
depressed
• Physical examination : Depressed;
markedly dehydrated; poor capillary refill.
• Problem list : 1. Thin, 2. Dehydrated.
Cell membrane
Diffusion
• The particles of a substance
dissolved in liquid or gas solvent are
in continuous random (Brownian)
movement. They tend to spread from
areas of high concentration is
uniform throughout the solution.
The net rate of diffusion
-Fick’s first law
• The net rate of diffusion
= -DA dc/dx
• D; diffusion coefficient
(base on radius)
• A; surface area
• dc/dx ; concentration gradient
• # if the molecule can diffuse faster than it
would be expected?  facilitate diffusion
Diffusion coefficient
• Einstein’s equation
D=KT/6∏rη
• K; Boltzmann constant
= 1.380662 X 10-23 J/K
• T; degrees Kelvin
(temperature of medium=C+273.16)
• R; molecular radius
• η; viscosity of medium
# mass∝r3, D ∝1/r
Ex) A:B=1:64(mass), 1:4(radius),
4:1(rate of diffusion)
Permeability coefficient
• J = -DA dc/dx = -DAβ (Co-Ci)/dx
=-Dβ/dx A(Co-Ci)
= -PA(Co-Ci)
• J; the net rate of diffusion
• β; partition coefficient -consider the lipid
solubility of the diffusing molecule
• β ∝ rate of diffusion
• Dβ/dx(P); permeability coefficient (consider the
both of lipid solubility and radius of molecule)
X50 partition coefficient
X50 diffusion rate (diethylurea)
Hydrophobic
(non_polar)
Non_ionized
Hydrophilic
(polar)
ionized
Diffusion &
Pharamacokinetics
• Most of drugs are absorbed by simple diffusion,
so lipid solubility is very important!
• ┌lipophilic(hydrophobic). non-polar
• └hydrophilic..... polar
• mostly ionization ↑ → polarity ↑
• ┌ionized - polar: hard to diffuse
• └non-ionized - non-polar: easy to diffuse
Henderson-Hasselbach
equation
• Weak acid(HA);
– pKa=pH + log([HA]/[A-])
• Weak base(BOH);
– pKa=pH + log([B+]/[BOH])
산모배속엔자식!
Examples
• Salycilic acid pKa=3
• luminal pH=8
• 3=8+log(NonIonized/Ionized)
log(NI/I)=-5
NI:I=1:100,000
•  very hard to diffuse through biological
membrane
티아무틴
폐에 혈중농도의 25배가 축적됩니다.
세포외액
세포내액
pH : 7.4
pH : 7.3
인지질의 이중 세포막
티아무틴 분자
티아무틴 분자
CO2
CO2
비이온화 분자
CO2
이온화 분자
CO2
CO2
가역적이지만 폐 조직내에 고농도로 축적됨
 세포막에 대한 약제의 능동적인 확산성(투과성)은 약제의 지용성 여부에 달려 있고,
비이온화된 약물의 형태는 지용성 상태이다. ( Tiamulin pKa is 7.4,weak basic)
Check
•
•
•
•
•
Weak base pka=7.4
Intracelluar pH=7.3
7.4=7.3+log[I/NI]
Log[I/NI]=0.1, I/NI=100.1
 1<100.1I > NI
Thank you for your attention ~