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| Pharmacokinetics |
药动学 |
| 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. |
药物要获得适宜的效应，就需要在作用部位达到适当的药物浓度。达到和维持适当药物浓度所需要的给药方案应该根据药物代谢动力学制定。适当的浓度和给药方案也取决于病人的临床状态、疾病的严重程度、有无并发疾病、其他药物使用情况以及其他因素。 |
| 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）. |
由于个体差异的存在，给药方案就须根据每一个病人的需要来设定。传统上的做法是凭经验不断调整剂量，一直到达到治疗目的为止。这种方法由于可能延误最佳药物效应或导致严重毒性反应，通常并不合适。另外一种做法是根据药物在某一病人体内的预期吸收和处置过程（分布和消除）用药，通过监测血浆药物浓度以及观察药物效应来调整用药剂量，采取这一做法，就必须懂得药代动力学，知道它是随病人年龄和体重而变化的，同时还要懂得并发疾病（如肾病、肝病、心血管疾病或其他并发疾病）的动力学后果。 |
| Basic Pharmacokinetic Parameters |
药物代谢动力学基本参数 |
| 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. |
大多数药物的药代动力学作用可用下列参数加以归纳。这些参数均为常数，但参数值也会因人而异，而且同一病人在不同情况下亦会有所不同。 |
| 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. |
生物利用度表示药物吸收进入体循环的分量。吸收速率常数表示吸收的速度。这些参数会影响单剂口服后的最大（峰）浓度，到达最大浓度的时间以及浓度-时间曲线下面积。在长期药物治疗期间，吸收的分量测量指标更重要，因为平均浓度就是根据它来计算的，而浓度的波动程度则与吸收速率常数有关。 |
| 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. |
表观分布容积是指使体内药物浓度与血液或血浆内浓度相等时所需要的液体容量。该参数可用以计算获得一定浓度所需的剂量及一定剂量后可达到的血浓度。非结合型药物浓度与药物效应密切相关，因此，非结合型分数是一个有用的测量指标，特别是当血浆蛋白结合改变时，如低蛋白血症、肾病、肝病引起的改变或药物相互置换作用引起的改变。表观分布容积和血浆非结合分数是药物分布中用得最广的参数。 |
| 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. |
药物从体内消除的速率随血浆浓度而改变。将消除速率和血浆浓度联系起来的参数就是总清除率。总清除率为肾清除率与肾外（经代谢）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. |
原型排泄分数有助于评估肾病或肝病对药物消除的潜在影响。低分数表明肝脏代谢很可能是药物的消除机制，因而，肝脏疾病可以影响药物的消除。肾脏疾病对高原型排泄分数药物的代谢动力学影响较大。 |
| 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（如肝脏）从血液中提取药物的速率不能超过药物输向该器官的速率，这样，清除率就有一个上限，不能脱离药物的输送，自然也不能脱离流入该器官的血流量。而且，当消除器官为肝脏和肠壁、药物又是口服时，部分药物在透过组织进入体循环之时就会被代谢，这一过程就称为首关代谢。如果一种药物在肝脏和肠壁的提取率（清除率）高，那么，它口服时的生物利用度就低，这时，就要避免口服给药，或在口服时要加大剂量，使其高于胃肠道外的用药剂量。首关代谢明显的药物包括：阿普洛尔、肼屈嗪、异丙肾上腺素、利多卡因、哌替啶、吗啡、硝苯地平、硝酸甘油、普萘洛尔、睾酮和维拉帕米。 |
| 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. |
消除速率常数是表示药物被消除器官从血液中清除及该药物在体内分布情况的一个函数。 |
| 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）是指血浆药物浓度或体内药物数量降低50%时所需的时间。对多数药物而言，不管它在体内有多少，它的半衰期都是相同的。只有苯妥英、茶碱和肝素是例外。 |
| 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, |
平均驻留时间（MRT）是表示药物消除的又一个测量值，是指某种药物快速静注后，其药物分子滞留在体内的平均时间。和清除率一样，它也不爱剂量的影响。快速静注后的平均驻留时间计算公式为： |
| 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是指一阶矩血浆浓度时间曲线下面积。对具有一室分布特征的药物来说，MRT等于消除速率常数的倒数。 |
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