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医学英语阅读:药物吸收

时间:2015-08-13 17:31点击:
Drug Absorption  药物吸收 
Process of drug movement from the administration site to the systemic circulation.  吸收是指药物由用药部位进入体循环的转运过程。 
Drug absorption is determined by physicochemical properties of drugs, their formulations, and routes of administration. Drug products--the actual dosage forms (eg, tablets, capsules, solutions), consisting of the drug plus other ingredients--are formulated to be administered by various routes, including oral, buccal, sublingual, rectal, parenteral, topical, and inhalational. A prerequisite to absorption is drug dissolution. Solid drug products (eg, tablets) disintegrate and deaggregate, but absorption can occur only after drugs enter solution.  药物的吸收是由药物的理化性质、药剂的配方及给药途径所决定的。药物制品,即一种药物的实际剂型(如片剂、胶囊剂、溶液剂),包含了药物本身及其他成分,配制后经不同途径服用,如口服、口腔、舌下、直肠、非肠道、局部和吸入等。吸收的先决条件是药物溶解。固体药物制品(如片剂)经过崩解和解聚,但其吸收则要等进入溶液后才能发生。 
Transport Across Cell Membranes  跨膜转运 
When given by most routes (excluding IV), a drug must traverse several semipermeable cell membranes before reaching the systemic circulation. These membranes are biologic barriers that selectively inhibit the passage of drug molecules and are composed primarily of a bimolecular lipid matrix, containing mostly cholesterol and phospholipids. The lipids provide stability to the membrane and determine its permeability characteristics. Globular proteins of various sizes and composition are embedded in the matrix; they are involved in transport and function as receptors for cellular regulation. Drugs may cross a biologic barrier by passive diffusion, facilitated passive diffusion, active transport, or pinocytosis.  采用大多数给药途径给药(静脉注射除外)的药物在进入体循环之前必须通过数层半渗透性细胞膜。这些细胞膜起着生物屏障的作用,有选择地抑制某些药物分子的通过。细胞膜主要由双分子的脂质基质构成,主要成份是胆固醇和磷脂。膜脂质使细胞膜具有稳定性,决定着细胞膜的渗透性特点。大小及组成各异的球形蛋白质就埋嵌在基质中,参与转运过程,发挥细胞调节受体的作用。药物可通过被动扩散、易化被动扩散、主动转运或胞饮作用等方式穿越生物屏障。 
Passive diffusion: In this process, transport across a cell membrane depends on the concentration gradient of the solute. Most drug molecules are transported across a membrane by simple diffusion from a region of high concentration (eg, GI fluids) to one of low concentration (eg, blood). Because drug molecules are rapidly removed by the systemic circulation and distributed into a large volume of body fluids and tissues, drug concentration in blood is initially low compared with that at the administration site, producing a large gradient.   被动扩散 在被动扩散过程中,跨细胞转运依赖于溶质浓度梯度。大多数药物分子以简单扩散方式从高浓度区(如胃肠液)透膜进入低浓度区(如血液)。由于药物分子是经体循环快速转运并分布到大容积体液和组织中去的,所以开始时,血液中的药物浓度低于给药部位的药物浓度,形成大的浓度梯度。 
The diffusion rate is directly proportional to the gradient but also depends on the molecule's lipid solubility, degree of ionization, and size and on the area of the absorptive surface. Because the cell membrane is lipoid, lipid-soluble drugs diffuse more rapidly than relatively lipid-insoluble drugs. Small molecules tend to penetrate membranes more rapidly than large ones.  扩散速率直接与梯度成正比,而且还依赖于药物分子的脂溶性、解离程度、分子量大小及吸收表面积。由于细胞膜为类脂质,脂溶性药物的扩散比相对的非脂溶性药物更快些,小分子的透膜速度也要比大分子快。 
Most drugs are weak organic acids or bases, existing in un-ionized and ionized forms in an aqueous environment. The un-ionized form is usually lipid soluble and diffuses readily across cell membranes. The ionized form cannot penetrate the cell membrane easily because of its low lipid solubility and high electrical resistance, resulting from its charge and the charged groups on the cell membrane surface. Thus, drug penetration may be attributed mostly to the un-ionized form. Distribution of an ionizable drug across a membrane at equilibrium is determined by the drug's pKa (the pH at which concentrations of un-ionized and ionized forms of the drug are equal) and the pH gradient, when present. For a weak acid, the higher the pH, the lower the ratio of un-ionized to ionized forms. In plasma (pH, 7.4), the ratio of un-ionized to ionized forms for a weak acid (eg, with a pKa of 4.4) is 1:1000; in gastric fluid (pH, 1.4), the ratio is reversed (1000:1). When the weak acid is given orally, the concentration gradient for un-ionized drug between stomach and plasma tends to be large, favoring diffusion through the gastric mucosa.   多数药物是弱有机酸或弱有机碱药物,他们以非解离或解离型态存在于水性环境中。非解离型部分通常为脂溶性,很容易透过细胞膜扩散。解离型则由于其脂溶性低,及其电荷和细胞膜表面带电荷基团所产生的高电阻,而不易透过细胞膜。因此,药物穿透主要是由非解离型来完成的。一种能解离的药物透过生物膜到达分布平衡取决于药物的pKa(药物的非解离型和解离型浓度相等时的pH)和当时的pH梯度。对一种弱酸性药物来说,pH值越高,非解离型与解离型之比就越低。如,在血浆中(pH7.4),某一种弱酸性药物(pKa为4.4)的非解离型与解离型之比是1:1000,在胃液中(pH1.4),其比率正好相反,为1000:1。当这种弱酸性药物经口服给药时,胃与血浆之间的非解离型药物浓度梯度很大,从而有利于透过胃粘膜扩散。 
At equilibrium, the concentrations of un-ionized drug in the stomach and in the plasma are equal because only un-ionized drug can penetrate the membranes; the concentration of ionized drug in the plasma would then be about 1000 times greater than that in the stomach. For a weak base with a pKa of 4.4, the outcome is reversed. Thus theoretically, weakly acidic drugs (eg, aspirin) are more readily absorbed from an acid medium (stomach) than are weak bases (eg, quinidine). However, whether a drug is acidic or basic, most of its absorption occurs in the small intestine.  在平衡状态下,只有非解离型药物能透过细胞膜,因此,非解离型药物在胃中和血浆中的浓度相等,而血浆中的解离型药物浓度则要比胃中高约1000倍。对一种pKa4.4的弱碱性药物来说,结果正好相反。因此,从理论上讲,弱酸性药物(如阿司匹林)在酸性介质中(胃腔)比弱碱性药物(如奎宁)更易吸收。然而,不管一种药物是酸性还是碱性,大多数吸收都是在小肠内进行的。 
Facilitated passive diffusion: For certain molecules (eg, glucose), the rate of membrane penetration is greater than expected from their low lipid solubility. One theory is that a carrier component combines reversibly with the substrate molecule at the cell membrane exterior, and the carrier-substrate complex diffuses rapidly across the membrane, releasing the substrate at the interior surface. Carrier-mediated diffusion is characterized by selectivity and saturability: The carrier transports only substrates with a relatively specific molecular configuration, and the process is limited by the availability of carriers. The process does not require energy expenditure, and transport against a concentration gradient does not occur.  易化被动扩散 某些分子(如葡萄糖)虽然脂溶性低,但透过细胞膜的速率却比预料的快,其中一个说法就是,有一种载体成分可以与底物分子在细胞膜外面进行可逆性结合,这种载体-底物复合物迅速扩散通过细胞膜,将底物释放在细胞膜内面。这种载体介导扩散具有选择性和饱和性特征。载体只转运那些具有特异性分子构型的底物。转动过程受有效载体数量控制。这种转运过程不消耗能量,也不会导致逆浓度梯度转运的发生。 
Active transport: This process is characterized by selectivity and saturability and requires energy expenditure by the cell. Substrates may accumulate intracellularly against a concentration gradient. Active transport appears to be limited to drugs structurally similar to endogenous substances. These drugs are usually absorbed from sites in the small intestine. Active transport processes have been identified for various ions, vitamins, sugars, and amino acids.  主动转运 这种转运过程的特征是选择性和饱和性,需要细胞的能量消耗。底物可以逆浓度梯度而积聚于细胞内。主动转运似乎只限于其结构类似于机体内源性物质的那些药物。他们通常经小肠特殊部位被吸收。现已确认,多种离子、维生素类、糖类和氨基酸类都采取这种主动转运方式。 
Pinocytosis: Fluid or particles are engulfed by a cell. The cell membrane invaginates, encloses the fluid or particles, then fuses again, forming a vesicle that later detaches and moves to the cell interior. This mechanism also requires energy expenditure. Pinocytosis probably plays a minor role in drug transport, except for protein drugs.  胞饮作用 胞饮指细胞呑入液体或微粒。细胞膜先内陷关住液体或微粒,然后再次加以融合,形成小泡,小泡随后脱离细胞膜进入细胞内。这种机制也需消耗能量。除蛋白质类药物外,胞饮在药物转运过程作用不大。