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Cell Biology 6 - transport 1st Sung Youn Lee, PhD. Student Veterinary collage, Room 320 02 450 3719, 016 293 6059 [email protected] 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<100.1I > NI Thank you for your attention ~