| Pharmacokinetics | 藥動學(xué) |
| An appropriate response to a drug requires the appropriate concentration of drug at the site of action. The dosage regimen required to attain and maintain the appropriate concentration depends on pharmacokinetics. The appropriate concentration and dosage regimen depend on the patient's clinical state, severity of the disorder, presence of concurrent disease, use of other drugs, and other factors. | 藥物要獲得適宜的效應(yīng)，就需要在作用部位達到適當(dāng)?shù)乃幬餄舛?。達到和維持適當(dāng)藥物濃度所需要的給藥方案應(yīng)該根據(jù)藥物代謝動力學(xué)制定。適當(dāng)?shù)臐舛群徒o藥方案也取決于病人的臨床狀態(tài)、疾病的嚴重程度、有無并發(fā)疾病、其他藥物使用情況以及其他因素?！?/td> |
| Because of individual differences, drug administration must be based on each patient's needs--traditionally, by empirically adjusting dosage until the therapeutic objective is met. This approach is frequently inadequate because optimal response may be delayed or serious toxic reactions may occur. Alternatively, a drug can be administered according to its expected absorption and disposition （distribution and elimination） in a patient, and dosage can be adjusted by monitoring plasma drug concentration and drug effects. This approach requires knowledge of the drug's pharmacokinetics as a function of the patient's age and weight and the kinetic consequences of concurrent diseases （eg, renal, hepatic, or cardiovascular disease or a combination of diseases）. | 由于個體差異的存在，給藥方案就須根據(jù)每一個病人的需要來設(shè)定。傳統(tǒng)上的做法是憑經(jīng)驗不斷調(diào)整劑量，一直到達到治療目的為止。這種方法由于可能延誤最優(yōu)藥物效應(yīng)或?qū)е聡乐囟拘苑磻?yīng)，通常并不合適。另外一種做法是根據(jù)藥物在某一病人體內(nèi)的預(yù)期吸收和處置過程（分布和消除）用藥，通過監(jiān)測血漿藥物濃度以及觀察藥物效應(yīng)來調(diào)整用藥劑量，采取這一做法，就必須懂得藥代動力學(xué)，知道它是隨病人年齡和體重而變化的，同時還要懂得并發(fā)疾病（如腎病、肝病、心血管疾病或其他并發(fā)疾?。┑膭恿W(xué)后果?！?/td> |
| Basic Pharmacokinetic Parameters | 藥物代謝動力學(xué)基本參數(shù) |
| The pharmacokinetic behavior of most drugs can be summarized by the following parameters. The parameters are constants, although their values may differ from patient to patient and in the same patient under different conditions. | 大多數(shù)藥物的藥代動力學(xué)作用可用下列參數(shù)加以歸納。這些參數(shù)均為常數(shù)，但參數(shù)值也會因人而異，而且同一病人在不同情況下亦會有所不同?！?/td> |
| Bioavailability expresses the extent of drug absorption into the systemic circulation. The absorption rate constant expresses the speed of absorption. These parameters influence the maximum （peak） concentration, the time at which the maximum concentration occurs （peak time）, and the area under the concentration-time curve （AUC） after a single oral dose. During long-term drug therapy, the extent of absorption is the more important measurement because average concentration depends on it; the degree of fluctuation is related to the absorption rate constant. | 生物利用度表示藥物吸收進入體循環(huán)的分量。吸收速率常數(shù)表示吸收的速度。這些參數(shù)會影響單劑口服后的最大（峰）濃度，到達最大濃度的時間以及濃度-時間曲線下面積。在長期藥物治療期間，吸收的分量測量指標更重要，因為平均濃度就是根據(jù)它來計算的，而濃度的波動程度則與吸收速率常數(shù)有關(guān)。 |
| The apparent volume of distribution is the amount of fluid that would be required to contain the drug in the body at the same concentration as in the blood or plasma. It can be used to estimate the dose required to produce a given concentration and the concentration expected for a given dose. The unbound concentration is closely associated with drug effects, so unbound fraction is a useful measure, particularly when plasma protein binding is altered--eg, by hypoalbuminemia, renal or hepatic disease, or displacement interactions. The apparent volume of distribution and the unbound fraction in plasma are the most widely used parameters for drug distribution. | 表觀分布容積是指使體內(nèi)藥物濃度與血液或血漿內(nèi)濃度相等時所需要的液體容量。該參數(shù)可用以計算獲得一定濃度所需的劑量及一定劑量后可達到的血濃度。非結(jié)合型藥物濃度與藥物效應(yīng)密切相關(guān)，因此，非結(jié)合型分數(shù)是一個有用的測量指標，特別是當(dāng)血漿蛋白結(jié)合改變時，如低蛋白血癥、腎病、肝病引起的改變或藥物相互置換作用引起的改變。表觀分布容積和血漿非結(jié)合分數(shù)是藥物分布中用得最廣的參數(shù)?！?/td> |
| The rate of elimination of a drug from the body varies with the plasma concentration. The parameter relating elimination rate to plasma concentration is total clearance, which equals renal clearance plus extrarenal （metabolic） clearance. | 藥物從體內(nèi)消除的速率隨血漿濃度而改變。將消除速率和血漿濃度聯(lián)系起來的參數(shù)就是總清除率。總清除率為腎清除率與腎外（經(jīng)代謝）清除率之和。 |
| The fraction excreted unchanged helps assess the potential effect of renal and hepatic diseases on drug elimination. A low fraction indicates that hepatic metabolism is the likely mechanism of elimination and that hepatic disease may therefore affect drug elimination. Renal diseases produce greater effects on the kinetics of drugs with a high fraction excreted unchanged. | 原型排泄分數(shù)有助于評估腎病或肝病對藥物消除的潛在影響。低分數(shù)表明肝臟代謝很可能是藥物的消除機制，因而，肝臟疾病可以影響藥物的消除。腎臟疾病對高原型排泄分數(shù)藥物的代謝動力學(xué)影響較大。 |
| The extraction rate of a drug from the blood by an eliminating organ, such as the liver, cannot exceed the rate of drug delivery to the organ. Thus, clearance has an upper limit, based on drug delivery and hence on blood flow to the organ. Furthermore, when the eliminating organ is the liver or gut wall and a drug is given orally, part of the dose may be metabolized as it passes through the tissues to the systemic circulation; this process is called first-pass metabolism. Thus, if extraction （clearance） of a drug is high in the liver or gut wall, oral bioavailability is low, sometimes precluding oral administration or requiring an oral dose much larger than an equivalent parenteral dose. Drugs with extensive first-pass metabolism include alprenolol, hydralazine, isoproterenol, lidocaine, meperidine, morphine, nifedipine, nitroglycerin, propranolol, testosterone, and verapamil. | 消除器官（如肝臟）從血液中提取藥物的速率不能超過藥物輸向該器官的速率，這樣，清除率就有一個上限，不能脫離藥物的輸送，自然也不能脫離流入該器官的血流量。而且，當(dāng)消除器官為肝臟和腸壁、藥物又是口服時，部分藥物在透過組織進入體循環(huán)之時就會被代謝，這一過程就稱為首關(guān)代謝。如果一種藥物在肝臟和腸壁的提取率（清除率）高，那么，它口服時的生物利用度就低，這時，就要避免口服給藥，或在口服時要加大劑量，使其高于胃腸道外的用藥劑量。首關(guān)代謝明顯的藥物包括：阿普洛爾、肼屈嗪、異丙腎上腺素、利多卡因、哌替啶、嗎啡、硝苯地平、硝酸甘油、普萘洛爾、睪酮和維拉帕米?！?/td> |
| The elimination rate constant is a function of how a drug is cleared from the blood by the eliminating organs and how the drug distributes throughout the body. | 消除速率常數(shù)是表示藥物被消除器官從血液中清除及該藥物在體內(nèi)分布情況的一個函數(shù)。 |
| Half-life （elimination） is the time required for the plasma drug concentration or the amount of drug in the body to decrease by 50%. For most drugs, half-life remains the same regardless of how much drug is in the body. Exceptions include phenytoin, theophylline, and heparin. | 半衰期（消除）是指血漿藥物濃度或體內(nèi)藥物數(shù)量降低50%時所需的時間。對多數(shù)藥物而言，不管它在體內(nèi)有多少，它的半衰期都是相同的。只有苯妥英、茶堿和肝素是例外?！?/td> |
| Mean residence time （MRT）, another measure of drug elimination, is the average time a drug molecule remains in the body after rapid IV injection. Like clearance, its value is independent of dose. After an IV bolus, | 平均駐留時間（MRT）是表示藥物消除的又一個測量值，是指某種藥物快速靜注后，其藥物分子滯留在體內(nèi)的平均時間。和清除率一樣，它也不愛劑量的影響?？焖凫o注后的平均駐留時間計算公式為： |
| MRT＝AUMC／AUC | MRT＝AUMC／AUC |
| AUMC is the area under the first moment of the plasma concentration-time curve. For a drug with one-compartment distribution characteristics, MRT equals the reciprocal of the elimination rate constant. | 其中AUMC是指一階矩血漿濃度時間曲線下面積。對具有一室分布特征的藥物來說，MRT等于消除速率常數(shù)的倒數(shù)。 |
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