酸枣仁油软胶囊新药开发研究.pptVIP

CHAPTER 3  Pharmacokinetics  （ body acts on drug ） A drug molecule moves from a side of membrane relatively high concentration to another side of low concentration without requiring energy, until an equilibrium has been achieved on both sides of the membrane. Nonionized form Ionized form  　 k1 [H+][A-]　 　 k1　 [H+][B] Ka＝──＝───── Ka＝──＝ ──── 　 k2 [HA] k2 [BH+]  　 [A] [B] pKa＝pH－log ─── pKa＝pH－log ─── [HA] [BH+]  [A-] 　 [B] pH－pKa＝log ─── pH－pKa＝log ─── [HA] [BH+]  weak acids weak bases ★ pH↑↓→[A-]↑↓ ★ pH↑↓→[BH+]↓↑ →ionization↑↓ →ionization↓↑ →lipid solution↓↑ →lipid solution↑↓ →permeation↓↑ →permeation↑↓ The passive movement of a drug across the membrane is facilitated by its special carrier. a. saturable process; b. special binding to the carrier; c. transport driven by concentration gradient without consuming energy. 2. Active transport (up hill) A drug molecule moves from a side of membrane relatively low to one of high concentration with requiring energy and special carrier. For example: penicillin and probenecid After glomerular filtration, penicillin undergoes tubular secretion (an active transport), having a very short half-life (t1/2=20~30 min). Probenecid having the same active mechanism can competitively inhibit the tubular secretion of penicillin. The t1/2 effects of penicillin are prolonged. 1. The routes of absorption 1) im or sc Absorption of drugs in solution through filtration from subcutaneous or intramuscular injection sites to blood