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五、简答题与计算题1.影响注射给药吸收的因素有哪些？怎样影响？2.比较药物主动转运与单纯扩散的异同。
3.计算题：某人静脉注射某药300mg后，其血药浓度（μg/ml）与时间（小时）的关系为C=60e-0.693t，试求：（1）该药的生物半衰期；（2）表观分布容积；（3）4小时后的血药浓度。
4.影响药物消化道吸收的理化因素有哪些？怎样影响？5.比较药物被动转运与媒体介导转运的异同。
6.计算题：给某患者静脉注射某药20mg，同时以20mg/h速度静脉滴注给药，问经过4h后体内血药浓度是多少？（已知：V=60L，t1/2=50h）7.影响药物皮肤给药的因素有哪些？怎样影响？8.药物的体内过程怎样？与药物疗效的关系怎样？9.计算题：某药口服后符合单室模型特征，已知：F=0.85,K=0.1h-1,Ka=1.0h-1,V=10L,口服剂量为250mg，求：t max、C max、AUC。
10.比较药物被动转运与媒体介导转运的异同。
11比较药物被动扩散与促进扩散的异同。
12已知某药物普通口服固体剂型生物利用度只有5%，与食物同服生物利用度可提高近一倍。
试分析影响该药物口服生物利用度的因素可能有哪些，拟采用哪种方法改善？13简述促进口服药物吸收的方法。
14决定药物被组织摄取和积蓄的主要因素是什么？哪些组织摄取药物最快？15为什么应用“表观分布容积”这一名词，表观分布容积有何意义?16药物血浆蛋白结合和组织蛋白结合对表观分布容积和药物消除有何影响？17请举例说明为什么弱碱性药物比弱酸性药物易透过血脑屏障？18影响微粒给药系统体内分布的因素有哪些？19影响肾小球滤过的因素有哪些？20大量出汗和大量失血，尿量会发生什么变化？变化的原因是什么？21试列举两个可以用于描述药物体内消除速度的动力学参数，并加以说明。
22一个病人静脉注射某药10mg，半小时后血药浓度是多少(已知t1/2=4h,V=60L)23某药物静脉注射给药80mg,立即测得血药浓度为10mg/ml,4h后血药浓度降为7.5mg/ml.求改药物的生物半衰期（假定药物以一定速度消除）24某药半衰期8h,表观分布容积为0.4L/kg,体重60kg的患者静脉注射600mg,注射后24h,消除的药量占给药剂量的百分比是多少？给药后24h的血药浓度为多少？25某药0至0.5h内尿中排出量为37.5mg,在0.25h血浆内药物浓度测定为10μg/ml,求CL r . 26已知磺胺嘧啶半衰期为16h,分布容积20L，尿中回收原形药物60%，求总清除率CL,肾清除率CL r ,并估算肝代谢清除率CL b .27某药物半衰期为40.8h，则该药物每天消除体内剩余药量的百分之几？28对某患者静脉滴注利多卡因，已知：t1/2=1.9h,V=100L,若要使稳态血药浓度达到4μg/ml,应取k0值为多少？29某一单室模型药物，生物半衰期为5h,静脉滴注达稳态血药浓度的95%，需要多少时间？30静脉注射给药后二室模型药物的血药浓度随时间下降有何特点？为什么?。
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血药浓度随时间变化的规律及药动学参数血药浓度随时间变化的规律及药动学参数（一）药时曲线用药后药物在体内的浓度可因转运或转化以致随时间而变化，药效也随着浓度而变化，如以曲线表示，则前者称时量关系曲线（Time-concentration Relationship Curve），后者为时效关系曲线（Time-response Relationship Curve）。
以非静脉一次给药为例，药物的时量关系和时效关系经历以下三个阶段：潜伏期－持续期－残留期。
潜伏期：用药后到开始出现作用的时间，反映药物的吸收和分布；持续期：药物维持有效浓度的时间；残留期：药物浓度已降至最小有效浓度以下时，但尚未从体内完全消除的时间。
（三）药物的消除动力学：血药浓度不断衰减的动态变化过程。
药物的消除：药物经生物转化和排泄使药理活性消失的过程。
药物的消除动力学有两种：1、一级消除动力学：指单位时间内药物按恒定的比例消除。
即血液中药物的消除速率与血中的药物浓度成正比，机体的血药浓度高，其单位时间内消除的药量多，消除速度随血药浓度下降而降低。
在血药浓度下降以后，药物的消除仍然按比率消除，故又称之为药物的恒比消除。
大多数药物按此方式消除。
如每小时消除1/2。
2、零级消除动力学：指单位时间内药物按恒定数量进行的消除。
即不论血浆药物浓度高低，单位时间内消除的药物量不变。
故又称之为药物的恒量消除。
常为药量过大，超过机体最大消除能力所致。
如每小时消除100mg/h。
（三）药物的消除动力学：血药浓度不断衰减的动态变化过程。
药物的消除：药物经生物转化和排泄使药理活性消失的过程。
药物的消除动力学有两种：1、一级消除动力学：指单位时间内药物按恒定的比例消除。
即血液中药物的消除速率与血中的药物浓度成正比，机体的血药浓度高，其单位时间内消除的药量多，消除速度随血药浓度下降而降低。
在血药浓度下降以后，药物的消除仍然按比率消除，故又称之为药物的恒比消除。
大多数药物按此方式消除。
时间依赖性与浓度依赖性抗菌药物的比较时间依赖性抗菌药物是指抗菌药物的抗菌效应主要取决于其血药浓度高于细菌的最低抑菌浓度（MIC）的时间，即当其血药浓度高于MIC时，其杀菌效应便达到了饱和状态，即使继续增加血药浓度，其杀菌效应不会相应增加。
这类药物主要包括β-内酰胺类、大环内酯类（阿奇霉素除外）、甲氧苄啶/磺胺甲恶唑、万古霉素、氯林可霉素与氟胞嘧啶类等[1]。
使用此类药物时，采取多次给药或持续静脉给药方案，可能会取得更好的疗效。
浓度依赖性抗菌药物是指抗菌药物的抗菌效应主要取决于其血药浓度高于MIC，具有浓度依赖性，即药物峰值浓度越高于MIC，其对致病菌的作用越强，作用速度也就越快。
这类药物主要包括甲硝唑、氨基糖苷类、喹诺酮类等[2]。
使用此类药物时，每日单次足量给药可有效提高抗菌疗效，同时可有效防止耐药菌株的产生、延长抗菌药物后效应（PAE）、降低毒性。
标签：时间依赖性；浓度依赖性；抗菌药物随着对药效动力学（Pharmacodynamics，PD）和药代动力学（Pharmacokinetics，PK）研究的进一步深入，研究者发现抗菌药物的抗菌疗效不仅取决于MIC，同时也与其药代动力学特点及PAE等密切有关。
根据PK/PD 特征，可将目前临床上应用的抗菌药物分为2类：时间依赖性抗菌药物（Time-dependent killers）和浓度依赖性抗菌药物（Concentration-dependent killers）。
这种分类方法与临床用药疗效、药物毒性的大小及用量用法的改变密切相关，同时对于指导临床上合理应用某些抗菌药物具有重要的临床意义。
1 抗菌药物后效应（PAE）PAE系指抗菌药物与其敏感致病菌短暂接触后，即使当其药物浓度下降到低于MIC或消除后，该致病菌仍受到持续抑制生长的效应。
PAE在不同药物、不同细菌持续时间有很大差异，其持续作用时间长短主要取决于抗菌药物的作用机制，同时还受抗菌药物浓度、作用时间等因素影响。
血药浓度随时间变化的规律及药动学参数（The regularity and pharmacokinetic parameters of serum concentration with time）The regularity and pharmacokinetic parameters of serum concentration with time(I) drug time curveAfter administration of drug concentration in vivo by transfer or transformation that is changing with time, effect also changes along with concentration, such as curve representation, the former is called curve relationship (Time-concentration Relationship Curve), the latter for the aging curve(Time-response Relationship Curve).Taking the non intravenous administration for example, the dose duration relationship and the time dependence of the drug pass through the following three stages: incubation period, duration, and residual period.Incubation period: the time after which medication starts to function, reflecting the absorption and distribution of drugs;Duration: the time at which an effective concentration of the drug is maintained;Residual period: the concentration of the drug has been reduced to below the minimum effective concentration, but has not yet been completely eliminated from the body.(three) elimination kinetics of drugs: the dynamic process ofcontinuous attenuation of serum concentration.Elimination of drugs: the process of biotransformation and excretion of drugs that results in the disappearance of pharmacological activity. There are two kinds of the kinetics of the elimination of drugs:1, first-order elimination kinetics: the elimination of drugs at a constant rate per unit time.That is, the rate of elimination of drugs in the blood is directly proportional to the concentration of drugs in the blood, the blood concentration of the body is high, the amount of drugs is eliminated in unit time, and the elimination rate decreases with the decrease of serum concentration. After the decrease in serum concentration, the elimination of the drug is still eliminated at a rate. Therefore, it is also called the constant ratio elimination of drugs. Most drugs are eliminated this way.Such as the elimination of 1/2 per hour.2. Zero elimination kinetics: the elimination of a constant amount of drugs per unit time. That is, regardless of the level of plasma drug concentration, the amount of drugs removed per unit time. It is also known as the quantity of drug elimination. Often too much, more than the maximum elimination capacity caused by the body.Such as the elimination of 100mg/h per hour.(three) elimination kinetics of drugs: the dynamic process of continuous attenuation of serum concentration.Elimination of drugs: the process of biotransformation and excretion of drugs that results in the disappearance of pharmacological activity. There are two kinds of the kinetics of the elimination of drugs:1, first-order elimination kinetics: the elimination of drugs at a constant rate per unit time.That is, the rate of elimination of drugs in the blood is directly proportional to the concentration of drugs in the blood, the blood concentration of the body is high, the amount of drugs is eliminated in unit time, and the elimination rate decreases with the decrease of serum concentration. After the decrease in serum concentration, the elimination of the drug is still eliminated at a rate. Therefore, it is also called the constant ratio elimination of drugs. Most drugs are eliminated this way.Such as the elimination of 1/2 per hour.2. Zero elimination kinetics: the elimination of a constant amount of drugs per unit time. That is, regardless of the level of plasma drug concentration, the amount of drugs removed per unit time. It is also known as the quantity of drug elimination. Often too much, more than the maximum elimination capacity caused by the body.Such as the elimination of 100mg/h per hour.Four 、 pharmacokinetic parameters of commonly used drugs(a) bioavailability (Bioavailability):.The speed and extent of absorption of drugs into the body circulation.Notation: F= (A/D) * 100% (oral: <100%; vein: 100%)Divided into: absolute bioavailability: F= (PO equal amount of drugs, AUC/iv equal amount of drugs AUC) * 100%The relative bioavailability of F= (equivalent to the reagent AUC/ with standard drug AUC * 100%)(two) apparent volume of distributionThe volume of fluid required for the distribution of plasma drug levels in vivo after the distribution of plasma and tissue is balanced. Vd=A/C0, theoretical capacity)Significance:1, the distribution volume of a given drug is measured to produce the desired dosage of the drug concentration: D = C, Vd2. Predict the distribution of drugs:Vd small drugs are mainly distributed in organs with large bloodflow;Vd large, low blood concentration and wide distribution of drugs;(three) half-life: generally refers to the half-life of plasma (T1/2), that is, the time required for the plasma concentration to fall by half. Since most drugs are eliminated in afirst-order kinetic manner, their half-life is a constant, T1/2=0.693/ke.Significance: reflects the rate of drug elimination. T1/2 long to eliminate slow and maintain long time(1) drug classification according to: short effect, medium effect, long effect;(2) determine the interval between dosing(3) the steady-state concentration time was predicted: 4-5 t1/2;(4) predict the basic elimination time of drugs: 4-5 t1/2 after the last dose(four) the steady blood concentration (CSS/ / Ping Ping concentration value): continuous constant drug dosages, gradually accumulated, through 5 half-life, blood concentration reached a stable level. The serum concentration at this time is called steady-state serum concentration, CSS. At this point the amount of drugs removed and the amount of drugsentering the body is equal, drugs are no longer accumulated in the body.Significance: (1) the plateau concentration is directly proportional to the total quantity of the day.(2) the fluctuation range of plateau concentration, high limit and low limit is proportional to each dose.(five) clearance rate:The rate of clearance of the drug is how many liters of blood can be removed per unit time. Each drug has its own fixed CL.CL=ke/Vd.Four 、 the change of serum concentration and the regimen of administrationIn clinical, most drugs need to be repeatedly given in order to achieve the desired level of serum concentration. Therefore, the time curve of the administration is zigzag.(1) continuous constant dose, total dose increases, CSS increases; administration of the same amount, change the number of drug CSS invariant. A total of conventional drugs in children, the same day the total number of drug, the more each use less, smaller fluctuations in safety range of small, multiple service, Ping concentration maintained at the minimum effective dose and minimum dose.(2) dose volume maintenance method: doubling the first dose, then rapidly reaching CSS in a half life, and then using maintenance dose. This method is suitable for emergency treatment, and requires rapid treatment.(3) intermittent administration: according to the needs of clinical treatment, the medication regimen with interval of more than half time can be used to reduce the incidence of adverse reactions. Such as glucocorticoids.(4) the regimen should be individualized, such as liver and kidney dysfunction, the half-life is longer than normal, and the time to CSS is longer. Therefore, the dosage should be reduced and the interval between doses should be extended.。
