国生一 Physiological factors 国生一 Physiological factors Components and properties of GI fluids. Components and properties of GI fluids. 国Gastric emptying胃排空 Gastric emptying Intestinal transit ④Intestinal transit ©Blood f1ow ©Blood f1ow 国f线一Physiological factors-GI fluids 国生Physiological factors-Gastric emptying pH value of GI fluids varies considerably along GIT. The gastric fluids are highly acidic,usually ranging from pH I to Gastric emptying influences the rate(and possibly the 3.5 extent)of absorption because it determines the .The pH of intestinal fluids gradually increases when moving in movement of drug from the stomach to the small the distal direction,ranging from approximately 5.7 to 7.7. intestine which is the best absorptive site for most drugs. The fluids in the large intestine are generally considered to have Gastric emptying pattemns are distinctly different, a pH of between 7 and 8. depending on the absence or presence of food. Gl fluids pH would infuence the drug solubility. permeability,and stability. 圈t笔Physiological factors-GIfluids ©it线一Gastri emptying-inthe absence of fod Various materials,particularly bile salts,enzymes,and mucin, In the absence of food,the empty stomach and the influence absorption. intestinal tract undergo a sequence of repetitious events referred to as the interdigestive migrating Bile salts,which are highly surface-active,may enhance the rate o notor complex(消化间期移行性复合运动)which is extent of absorption of poorly waer-soluble drugs by increasing the composed of four stages at a period of 2 hours. rate of dissolution in the Gl fluids. .Stage 1:minimal activity,about Ih. Bile salts may also reduce drug absorption through the formation of water-insoluble,nonabsorbable complex. Stage 2:irregular contractions that gradually increase in strength,30-45 min. Some enzymes may act with some drugs. .Stage 3:intense peristaltic waves that result in the emptying Mucin,a viscous mucopolysaccharide that lines and protects and the of gastric contents,5-15 min.(housekeeper waves) inestinal epithelm,has been thoughtto bind rug Stage 4:a transition of decreasing activity,leading to the beginning of the next cycle. 77 Shanghai Jiao Tong University Physiological factors Components and properties of GI fluids. Gastric emptying胃排空 Intestinal transit Blood flow Shanghai Jiao Tong University Physiological factors-GI fluids pH value of GI fluids varies considerably along GIT. • The gastric fluids are highly acidic, usually ranging from pH 1 to 3.5. • The pH of intestinal fluids gradually increases when moving in the distal direction, ranging from approximately 5.7 to 7.7. • The fluids in the large intestine are generally considered to have a pH of between 7 and 8. GI fluids pH would influence the drug solubility, permeability, and stability. Shanghai Jiao Tong University Physiological factors-GI fluids Various materials, particularly bile salts, enzymes, and mucin, influence absorption. • Bile salts, which are highly surface-active, may enhance the rate or extent of absorption of poorly water-soluble drugs by increasing the rate of dissolution in the GI fluids. • Bile salts may also reduce drug absorption through the formation of water-insoluble, nonabsorbable complex. • Some enzymes may act with some drugs. • Mucin, a viscous mucopolysaccharide that lines and protects and the intestinal epithelium, has been thought to bind certain drugs nonspecifically, prevent or reduce absorption. Shanghai Jiao Tong University Physiological factors Components and properties of GI fluids. Gastric emptying Intestinal transit Blood flow Shanghai Jiao Tong University Physiological factors-Gastric emptying Gastric emptying influences the rate (and possibly the extent) of absorption because it determines the movement of drug from the stomach to the small intestine which is the best absorptive site for most drugs. Gastric emptying patterns are distinctly different, depending on the absence or presence of food. Shanghai Jiao Tong University Gastric emptying-in the absence of food In the absence of food, the empty stomach and the intestinal tract undergo a sequence of repetitious events referred to as the interdigestive migrating motor complex(消化间期移行性复合运动) which is composed of four stages at a period of 2 hours. • Stage 1: minimal activity, about 1h. • Stage 2: irregular contractions that gradually increase in strength, 30-45 min. • Stage 3: intense peristaltic waves that result in the emptying of gastric contents, 5-15 min. (housekeeper waves) • Stage 4: a transition of decreasing activity, leading to the beginning of the next cycle