口服給藥的介紹

　　口服給藥(administering oral medications)是藥物療法最常采用的給藥方式，藥物經(jīng)胃腸道黏膜吸收。接下來小編為大家整理口服給藥的介紹，希望對你有幫助哦!

　　For oral administration, the most common route, absorption refers to the transport of drugs across membranes of the epithelial cells in the GI tract. Absorption after oral administration is confounded by differences in luminal pH along the GI tract, surface area per luminal volume, blood perfusion, the presence of bile and mucus, and the nature of epithelial membranes. Acids are absorbed faster in the intestine than in the stomach, apparently contradicting the hypothesis that un-ionized drug more readily crosses membranes. However, the apparent contradiction is explained by the larger surface area and greater permeability of the membranes in the small intestine.

　　口服是最常用的給藥途徑，其吸收涉及藥物通過胃腸道上皮細胞膜的轉(zhuǎn)運。由于給藥時相關環(huán)境條件的不同，如胃腸道管腔內(nèi)pH及單位腔道容積的表面積，組織血流灌注情況，膽汁和粘液的存在以及上皮細胞膜的性質(zhì)等，口服給藥的吸收也有差異。酸性藥物在腸中的吸收較胃中快，這顯然與非解離藥物更易透過細胞膜這一假設相矛盾。然而，這種明顯的矛盾卻可以從小腸具有很大的表面積和小腸細胞膜具有較大的通透性中得到答案。

　　The oral mucosa has a thin epithelium and a rich vascularity that favors absorption, but contact is usually too brief, even for drugs in solution, for appreciable absorption to occur. A drug placed between the gums and cheek (buccal administration) or under the tongue (sublingual administration) is retained longer so that absorption is more complete.

　　口腔粘膜上皮很薄，血管豐富，有利于藥物吸收。但是，接觸的時間太短暫，即使是溶液劑也來不及等到明顯的吸收發(fā)生。把一種藥物置于齒齦和面頰之間(頰部給藥)或置于舌下(舌下給藥)則可保留較長時間，使吸收更加完全。

　　The stomach has a relatively large epithelial surface, but because it has a thick mucous layer and the time that the drug remains there is usually relatively short, absorption is limited. Absorption of virtually all drugs is faster from the small intestine than from the stomach. Therefore, gastric emptying is the rate-limiting step. Food, especially fatty foods, slows gastric emptying (and the rate of drug absorption), explaining why some drugs should be taken on an empty stomach when a rapid onset of action is desired. Food may enhance the extent of absorption for poorly soluble drugs (eg, griseofulvin), reduce it for drugs degraded in the stomach (eg, penicillin G), or have little or no effect. Drugs that affect gastric emptying (eg, parasympatholytic drugs) affect the absorption rate of other drugs.

　　胃具有相對大的上皮表面，但由于它有較厚的粘液層，而且藥物在胃內(nèi)停留的時間相對較短，吸收也較少。事實上，所有藥物在小腸中的吸收速度都要比胃中快。因此，胃排空即是一限速性步驟。食物，特別是脂類食物，延緩胃排空速度(從而也延緩藥物吸收速度)，這也就是為何某些希望迅速奏效的藥物宜空腹服用的原因。食物可增強某些溶解性差的藥物(如灰黃霉素)的吸收，減少胃內(nèi)降解藥物(如青霉素G)的吸收，食物以裁縫折吸收或無影響，或影響甚少。影響胃排空的藥物(如副交感神經(jīng)阻斷劑)可影響其他藥物的吸收速度。

　　The small intestine has the largest surface area for drug absorption in the GI tract. The intraluminal pH is 4 to 5 in the duodenum but becomes progressively more alkaline, approaching 8 in the lower ileum. GI microflora may inactivate certain drugs, reducing their absorption. Decreased blood flow (eg, in shock) may lower the concentration gradient across the intestinal mucosa and decrease absorption by passive diffusion. (Decreased peripheral blood flow also alters drug distribution and metabolism.)

　　小腸在胃腸道中具有最大的藥物吸收表面積。十二脂腸腔內(nèi)pH值為4~5，管腔內(nèi)pH值趨堿性逐漸增強，至回腸下部時pH接近8。胃腸道內(nèi)的菌叢可使某些藥物失活，降低藥物的吸收。血流量的減少(如休克病人)可以降低跨腸粘膜的濃度梯度，從而減少被動擴散吸收。(外周血流減少也會改變藥物的分布和代謝。

　　Intestinal transit time can influence drug absorption, particularly for drugs that are absorbed by active transport (eg, B vitamins), that dissolve slowly (eg, griseofulvin), or that are too polar (ie, poorly lipid-soluble) to cross membranes readily (eg, many antibiotics). For such drugs, transit may be too rapid for absorption to be complete.

　　腸道通過時間　腸道通過時間能影響藥物吸收，特別是經(jīng)主動轉(zhuǎn)運吸收的藥物(如維生素B)、溶解緩慢的藥物(如灰黃霉素)，或極性太高(即脂溶性差)難以透過細胞膜的藥物(如許多抗生素)。這類藥物通過太快，致使吸收不全。

　　For controlled-release dosage forms, absorption may occur primarily in the large intestine, particularly when drug release continues for > 6 h, the time for transit to the large intestine.

　　對控釋劑型來說，吸收主要在大腸內(nèi)進行，特別是藥物釋放時間超過6小時，也就是藥物運達大腸的時間。

　　Absorption from solution: A drug given orally in solution is subjected to numerous GI secretions and, to be absorbed, must survive encounters with low pH and potentially degrading enzymes. Usually, even if a drug is stable in the enteral environment, little of it remains to pass into the large intestine. Drugs with low lipophilicity (ie, low membrane permeability), such as aminoglycosides, are absorbed slowly from solution in the stomach and small intestine; for such drugs, absorption in the large intestine is expected to be even slower because the surface area is smaller. Consequently, these drugs are not candidates for controlled release.

　　溶液劑型的吸收　藥物吸收受到大量胃腸道內(nèi)分泌液的影響。藥物要想被吸收，就必須要在與低pH環(huán)境及潛在的降解酶的接觸中生存下來。通常，即使某種藥物在腸環(huán)境中很穩(wěn)定，但進入大腸的仍然是極少數(shù)。低親脂性(即膜通透性低)藥物，如氨基糖苷類，經(jīng)胃和小腸溶液被緩慢吸收。而在大腸中，因表面積更小，預期吸收更慢。因此，這些藥物不宜制成控釋劑型。

　　Absorption from solid forms: Most drugs are given orally as tablets or capsules primarily for convenience, economy, stability, and patient acceptance. These products must disintegrate and dissolve before absorption can occur. Disintegration greatly increases the drug's surface area in contact with GI fluids, thereby promoting drug dissolution and absorption. Disintegrants and other excipients (eg, diluents, lubricants, surfactants, binders, dispersants) are often added during manufacture to facilitate these processes. Surfactants increase the dissolution rate by increasing the wetability, solubility, and dispersibility of the drug. Disintegration of solid forms may be retarded by excessive pressure applied during the tableting procedure or by special coatings applied to protect the tablet from the digestive processes of the gut. Hydrophobic lubricants (eg, magnesium stearate) may bind to the active drug and reduce its bioavailability.

　　固體劑型的吸收　主要是出于方便、經(jīng)濟、藥物穩(wěn)定性、及病人接受性的考慮，大多數(shù)藥物都以片劑或膠囊劑口服給藥。這些制劑必須經(jīng)過崩解和溶解才能被吸收。崩解大大增加了藥物與胃腸液的接觸表面積，從而促進藥物的溶解和吸收。在制藥過程中,為了促進崩解和溶解作用，往往添加一些崩解劑和其他賦形劑(如稀釋劑、潤滑劑、表面活性劑、粘合劑、分散劑)。表面活性劑通過增加藥物的吸濕性、溶解度和分散性來增加其溶解速率。在制片過程中壓片壓力過大，或為了使藥片免受腸道消化作用的影響而使用特殊的包衣，可延緩固體劑型的崩解。忌水性潤滑劑(如硬脂酸鎂)可與活性藥物結(jié)合而降低其生物利用度。

　　Dissolution rate determines the availability of the drug for absorption. When slower than absorption, dissolution becomes the rate-limiting step. Overall absorption can be controlled by manipulating the formulation. For example, reducing the particle size increases the drug's surface area, thus increasing the rate and extent of GI absorption of a drug whose absorption is normally limited by slow dissolution. Dissolution rate is affected by whether the drug is in salt, crystal, or hydrate form. The Na salts of weak acids (eg, barbiturates, salicylates) dissolve faster than their corresponding free acids regardless of the pH of the medium. Certain drugs are polymorphic, existing in amorphous or various crystalline forms. Chloramphenicol palmitate has two forms, but only one sufficiently dissolves and is absorbed to be clinically useful. A hydrate is formed when one or more water molecules combine with a drug molecule in crystal form. The solubility of such a solvate may markedly differ from the nonsolvated form; eg, anhydrous ampicillin has a greater rate of dissolution and absorption than its corresponding trihydrate.

　　溶解速率　溶解速率決定藥物吸收時的可用度。當溶解速率低于吸收速率時，溶解就會制約吸收。藥物的總體吸收可通過改變配方來加以調(diào)控，例如，減小顆粒體積可增加藥物的表面積，從而增加那些溶解緩慢吸收受限的藥物的胃腸道吸收速率和分量。藥物的不同形式，如鹽、晶體或水合物等，都可影響溶解速率。不管介質(zhì)的pH是多少，弱酸的鈉鹽(如巴比妥酸鹽，水楊酸鹽)比其相應的游離酸溶解得快。某些藥物有多種形態(tài)，可以非晶體形或不同晶體形存在。棕櫚酸氯霉素有兩種存在形態(tài)，但只有一種形態(tài)能充分溶解吸收，也因而被臨床使用。當一個或多個水分子和一個晶體形藥物分子相結(jié)合時，就構(gòu)成一種水合物。這種的溶解度可能與非水合物的溶解度有明顯的不同。例如，無水氨芐西林的溶解速率和吸收比其它相應水合物的溶解吸收速率都要快得多。