国生 圈丛生一 Physicochemical factors-pK Physicochemical factors Most drugs,whether ionized or nonionized(i.e., regardless of pH),are best absorbed from the small ·Dissolution intestine as a result of the large absorbing surface Oil/water partition coefficient area of this region. ·pKa 。Molecular weight 国生一 Physicochemical factors-pK 国话生一 Most drug molecules are either weak acids or bases Physicochemical factors that will ionized to an extent determined by the compound's pKa and the pH of the biological fluid ·Dissolution in which it is dissolved. Oil/water partition coefficient The importance of ionization in drug absorption is ·pKa based on the observation that the nonionized form of ·Molecular weight the drug has a greater Ko/w. 圈生一 Physicochemical factors-pK Physicochemical factors-MW 国pH-partition hypothesis pH分配假说 Passive absorption in the gastrointestinal tract is lonizable compounds penetrate biological membranes severely limited by the size of the penetrating drug primarily in the nonionized form.As a result,acidic molecule. drugs should best be absorbed from acidic solutions for The optimal molecular weight is less than 500. which pH <pK,whereas basic compounds would best be absorbed from alkaline solutions for which pH pKa 66 Shanghai Jiao Tong University Physicochemical factors • Dissolution • Oil/water partition coefficient • pKa • Molecular weight Shanghai Jiao Tong University Physicochemical factors-pKa Most drug molecules are either weak acids or bases that will ionized to an extent determined by the compound’s pKa and the pH of the biological fluid in which it is dissolved. The importance of ionization in drug absorption is based on the observation that the nonionized form of the drug has a greater Ko/w. Shanghai Jiao Tong University Physicochemical factors-pKa pH-partition hypothesis pH分配假说 • Ionizable compounds penetrate biological membranes primarily in the nonionized form. As a result, acidic drugs should best be absorbed from acidic solutions for which pH ＜pKa, whereas basic compounds would best be absorbed from alkaline solutions for which pH＞ pKa. Shanghai Jiao Tong University Physicochemical factors-pKa Most drugs, whether ionized or nonionized (i.e., regardless of pH), are best absorbed from the small intestine as a result of the large absorbing surface area of this region. Shanghai Jiao Tong University Physicochemical factors • Dissolution • Oil/water partition coefficient • pKa • Molecular weight Shanghai Jiao Tong University Physicochemical factors-MW Passive absorption in the gastrointestinal tract is severely limited by the size of the penetrating drug molecule. The optimal molecular weight is less than 500