1、1 Simple diffusionl Passive process, concentration gradient dependent, requires no energyl Molecules move from area of high to low concentrationl Rate of diffusion is proportional to:1.lipid solubility, the greater the lipid solubility the faster the rate of diffusion2.pKa of molecules3.Concentratio
2、n difference between both sides(Diffusion through lipid bi-layerAcidic drug: HA H+ + A (ionized) Basic drug: BH+ H+ + B (unionized)Ion trapping( Cell membranes are less permeable to ionized compounds H+HA A-HAH+A-B BH+H+H+B BH+Ka = H+ A HApKa = pH - log A HA A HA10 pH-pKa =Acidic drug：Ionization dep
3、ends on pH and pKaBasic drug： pKa-pHA + H+HAHAH+ + A A HA10pH-pKa =Plasma： pH=7Stomach： pH=411 102 105Cromolyn Sodium (色 甘酸 钠 ) pKa=2, Acidic= 107-2 = 105 A HA10pH-pKa = 104-2 = 102TotalTotalExample101 100001( Small molecules diffusion through aqueous channels2. Filtrationn Water solubilityn Small m
4、olecular Diameter of aqueous channels in Capillary wall: 4-8（ =1010m )Only for water, urea filtration 100 not permeableIntracellular cleft: 40, all solute in blood are permeable except proteinIntracellular cleftIntracellular cleft: big hole3. Carrier-mediated transportActive transportl Against conce
5、ntration gradient l Requires coupling of energy (hydrolysis of ATP) Facilitated diffusionl Along concentration gradient l Requires no energy1. Requiring carrier 2. Structure specific3. Saturable (functional protein molecules are limited)4. Competitive inhibitionDisposition of drug in the bodyAbsorpt
6、ion, Distribution, Metabolism and ExcretionSection 2Ch. 2( Transfer of a drug from its site of administration to the blood streamOral ingestionMajor site:l Longer transit time = 3 hours l Larger surface area of villusl Abundant blood flow l pH5-8 good for most of drugsintestine1 Absorptionl Oral cavity 0.5-l .0 m2l Stomach 0.1-0.2 m2 l Small intestine 100 m2l Large intestine 0.04-0.07 m2l Rectum 0.02 m2Ficks Law of DiffusionFlux (molecules per unit time) (C1 C2) AreaPermeability coefficientThickness
