翻译7

The therapeutic response of a drug is normally dependent on an adequate concentration of the

drug being achieved and then maintained at the site or sites of action of the drug. In the case of

systemically acting drugs (i.e. drugs that reach these sites via the systemic circulation), it is

generally accepted for clinical purposes that a dynamic equilibrium exists between the

concentration of drug at its site(s) of action and the concentration of drug in blood plasma. An

important consequence of this dynamic equilibrium is that it permits a therapeutically effective

concentration of drug to be achieved at its site(s) of action by adjustment of the concentration of

drug in blood plasma.

药物的治疗反应通常是依赖于适当的药物达到并保持在该位点或药物的作用部位的浓度。在全身作用药物的情况下（即药物通过全身血液循环达到这些位点），它是公认的临床用途，在其部位的药物浓度之间存在一种动态平衡的作用和血浆中的药物浓度。这种动态平衡的一个重要后果是，它允许一个治疗有效药物浓度保持在其位点实现的血药浓度的调节作用。

Strictly speaking, the concentration of drug in plasma water (i.e. protein-free plasma) is a more

accurate index of drug concentration at the site(s) of action than the concentration of drug in

whole plasma since a drug may often bind in a reversible manner to plasma protein. Only drug

which is unbound (i.e. dissolved in plasma water) can pass out of the plasma through the

capillary endothelium and reach other body fluids and tissues and hence its site(s) of action. Drug

concentration in whole blood is also not considered to be an accurate indirect index of the

concentration of drug at its site(s) of action since drug can bind to and enter blood cells.

严格地说，血浆（即水无蛋白血浆）中的药物浓度是药物浓度更准确的指标对比于当药物往往结合在一个可逆的血浆蛋白在血浆药物时的浓度。只有药物是未结合（即溶解在血浆中的水）可以从血浆通过毛细血管内皮细胞渗透到其他体液和组织中，在它的位点起作用。由于药物可以结合并进入细胞，所以血液中的药物浓度也不被认为是在其作用部位的药物浓度准确的间接指标。

However, to measure the concentration of an unbound drug in plasma water requires more

complex and sensitive assay methods than to measure the total concentration of both unbound

and bound drug in total plasma. Thus, for clinical purposes, drug concentration in blood plasma is

usually measured and is regarded as an index of drug concentration at the site(s) of action of the

drug and of the clinical effects of the drug. However, it should be realized that this is a

simplification and may not always be valid. Indeed one should not draw inferences about the

clinical effects of a drug from its plasma concentration until it has been established that the two

are consistently correlated.

然而，衡量一个非结合药物在血浆中的浓度比测量未结合的和总血浆结合药物的总浓度需要更复杂的和敏感的检测方法。因此，临床用途，血药浓度的测量通常是被认为是在作用部位的药物浓度指数以此来衡量药物的作用和药物的临床疗效。然而，应该认识到，这是一个简化和可能并不总是有效的。我们的确不应该从药物的血浆浓度的临床效果来推论，除非两者已建立了相关关系。

It has been assumed that the plasma drug concentration is directly proportional to the clinical

effect of that drug.

The concentration of drug in blood plasma depends on numerous factors. These include

the relative amount of an administered dose that enters the systemic circulation, the rate at

which this occurs, the rate and extent of distribution of the drug between the systemic circulation

and other tissues and fluids and the rate of elimination of the drug from the body.

血浆药物浓度已被假定为与该药物的临床效果成正比。

血浆中药物的浓度取决于许多因素。这些包括一个剂量进入体循环的相对量，该反应发生的速率，药物分布在循环系统的速率和程度和其他组织和体液和体内的药物消除率。

Apart from the intravenous route of drug administration, where a drug is introduced directly

into the blood circulation, all other routes of administering systemically acting drugs involve the

absorption of drug from the place of administration into the blood.1 Drug must be absorbed in a

sufficient quantity and at a sufficient rate in order to achieve a certain blood plasma

concentration which, in turn, will produce an appropriate concentration of drug at its site(s) of

action to elicit the desired therapeutic response.

除了药物静脉给药，当药品被直接进入血液循环系统作用的时候，所有其他方式的全身作用的给药都涉及药物如何从给药位置到达血液。药物必须吸收足够量和有足够的速度才能达到一定的血浆浓度，反过来，通过在其位点上产生一个适当的药物浓度的行为来得到想要的治疗作用。

It follows that there are two aspects of drug absorption which are important in clinical

practice, namely, the rate and the extent to which the administered dose is absorbed. Simply

because a certain dose of a drug is administered to a patient，there is no guarantee (except for

intravenous administration) that all of that dose will reach the systemic circulation. The fraction

of an administered dose of drug that reaches the systemic circulation in unchanged form is

known as the bioavailable dose.

因此，药物的吸收在临床实践中有很重要的两个方面，即吸收剂量的速率和程度。因为给病人服用一定剂量的药物，不能保证（除静脉给药）所有的剂量都达到全身血液循环。药物到达体循环而不发生变性的剂量被称为生物有效剂量。

The relative amount of an administered dose of a particular drug which reaches the systemic

circulation intact and the rate at which this occurs is known as the bioavailability of that drug.

Bioavailability is thus concerned with the quantity and the rate at which the intact form of a

particular drug appears in the systemic circulation following administration of that drug. The

bioavailability exhibited by a drug is thus very important in determining whether a

therapeutically effective concentration is achieved at the site(s) of action of the drug.

给的特定药物的相对量通过完整的全身循环的这种情况被称为该药物的生物利用度。生物利用度也因此涉及给定特定药物在给药后出现在体循环时的速度和量，一种药物的生物利用度对于决定药物在作用位点是否达到有治疗效果的浓度是非常重要的。

In defining bioavailability in these terms it is assumed that intact drug is the

therapeutically active form of the drug. This definition of bioavailability would not be valid in the

case of a pro¬drug, whose therapeutic action normally depends on it being converted into its

therapeutically active form prior to or on reaching the systemic circulation. It should also be

noted that in the context of bioavailability, the term systemic circulation refers primarily to

venous blood (excluding the hepatic portal blood during the absorption phase) and arterial blood

which carries the intact drug to the tissues.

在确定生物利用度在这些方面则认为完整的药物是药物的治疗活性。生物利用度这一定义在前体药物的情况下是无效的，其治疗作用通常取决于在全身循环之前或循环时它被转换成它有治疗活性的形式。还应指出的是，生物利用度的情况下，循环系统主要是指完整的药物通过静脉血（不包括肝门静脉的血液在吸收阶段）和动脉血到达组织。

Hence according to the definition of bioavailability, an administered dose of a particular

drug in an oral dosage form will be 100% bioavailable only if the drug is completely released from

the dosage form into solution in the gastrointestinal fluids.2 The released drug must also be

completely stable in solution in the gastrointestinal fluids and all of the drug must pass through

the gastrointestinal barrier into the mesenteric circulation without being metabolized. Finally, all

of the absorbed drug must pass into the systemic circulation without being metabolized on

passing through the liver.

Hence according to the definition of bioavailability, an administered dose of a particular drug in

an oral dosage form will be 100% bioavailable only if the drug is completely released from the

dosage form into solution in the gastrointestinal fluids.2 The released drug must also be

completely stable in solution in the gastrointestinal fluids and all of the drug must pass through

the gastrointestinal barrier into the mesenteric circulation without being metabolized. Finally, all

of the absorbed drug must pass into the systemic circulation without being metabolized on

passing through the liver.

因此，根据生物利用度的定义，对于一个特定的药物的口服剂型的剂量，如果药物是完全释放在胃肠液的溶液的剂型，该药物将是100%的生物利用度。释放的药物必须在胃肠液的溶液中是完全稳定的，所有的药物都必须通过通过胃肠屏障进入肠系膜循环不被代谢。最后，所有的药品必须通过吸收进入全身血液循环而不经过肝脏代谢。

Thus any factor which adversely affects either the release of the drug from the dosage form, its

dissolution in the gastrointestinal fluids, its stability in the gastrointestinal fluids, its permeation

through and stability in the gastrointestinal barrier or its stability in the hepatic portal circulation

will influence the bioavailability exhibited by that drug from the dosage form in which it was

administered.

因此任何影响从剂型中释放该药物的因素，包括其在胃肠液中溶解，在胃肠液中的稳定性，其渗透并稳定在胃肠道屏障稳定在或肝门脉循环中，都会使影响药物的给药剂量的生物利用度。

Biopharmaceutics （生物药剂学）

Many factors have been found to influence the time course of a drug in the plasma and

hence at its site(s) of action. These include the foods eaten by the patient, the effect of the

disease state on drug absorption, the age of the patient, the site(s) of absorption of the

administered drug, the coadministration of other drugs, the physical and chemical properties of

the administered drug, the type of dosage form, the composition and method of manufacture of

the dosage form and the size of dose and frequency of administration of the dosage form.

很多因素影响了药物进入血浆的时间因此影响它作用在位点，包括病人吃的食物，疾病状态对药物吸收的影响，病人的年龄，作用位点的吸收，同时服用其他药物，药物的物理和化学性质，剂型的类型，药剂的制造方式和成份以及给药的频率和剂量。

Thus, a given drug may exhibit differences in its bioavailability if it is administered in the same

type of dosage form by different routes of administration, e.g. an aqueous solution of a given

drug administered by the oral and intramuscular routes of administration. A given drug may also

show differences in its bioavailability from one type of dosage form to another when given by the

same route, e.g. a tablet, a hard gelatin capsule and an aqueous suspension administered by the

peroral route.

因此，如果是使用相同类型的剂型，通过不同的给药途径，例如某一特定药物通过口服和肌肉注射给药途径，一个特定的药物可能有不同的生物利用度。一个给定的药物从一个类型的剂型到另一个时，相同的给药途径，其生物利用度也有差异，例如片剂，硬胶囊和口服途径给药的水悬浮液。

A given drug might show different bioavailabilities from different formulations of the

same type of dosage form given by the same route of administration, e.g. different formulations

of an aqueous suspension of a given drug administered by the peroral route. Variability in the

bioavailability exhibited by a given drug from different formulations of the same type of dosage

form or from different types of dosage forms etc., can cause patients to be under-or

overmedicated. The result may be therapeutic failure or serious adverse effects particularly in the

case of drugs which have a narrow therapeutic range.

一个给定的药物通过不同的配方但相同的类型和相同的给药途径也可能有不同的生物利用度，例如不同剂型的药物的口服途径给药的含水悬浮液。生物利用度的变化性表现为给定药物的不同配方的相同或不同剂型等，有可能导致患者用药不足或用药过量。结果可能是治疗失败或严重的不利影响，特别是在使用的药物有一个狭窄的治疗范围的情况下。

The entry of a drug into the systemic circulation following the administration of a drug product

usually involves:

1. the release of the drug from its dosage form into solution in the biological fluids at the

absorption site, and

2. the movement of the dissolved drug across biological membranes into the systemic

circulation.

The study of the various factors which can affect these processes and the application of

this knowledge to obtain the expected therapeutic effect from a drug product when it is used by

a patient are known as biopharmaceutics.

一种药物在给药后进入体循环的途径包括：1，在吸收部位药物从药剂释放进入生物体液，2溶解的药物通过生物膜进入全身血液循环的运动。对它的研究可以获得影响这些过程的各种因素和应用这方面的知识获得由病人使用时预期的治疗效果被称为生物药剂学。