DiPiro J T
Department of Pharmacy, University of Georgia College of Pharmacy, Augusta.
Am J Med. 1989 Aug 16;87(2A):31S-35S. doi: 10.1016/0002-9343(89)90111-3.
Influences that determine a drug's effects include pharmacokinetic factors (the serum concentrations of drug as determined by the drug dose, absorption, distribution, and excretion) and pharmacodynamic factors (the intensity of drug effect). Most assessments of drug effect focus on the therapeutic range, i.e., the serum concentrations below which therapeutic effects are unlikely and above which toxic effects may be seen. A goal for many treatment regimens is to maintain serum drug concentrations within the therapeutic range. Maintenance of drug concentrations within the therapeutic range can be difficult with many traditional oral dosage formulations. Soon after administration of standard tablets, capsules, or liquids, a pronounced peak level is observed in serum. At the end of a dosage interval, serum concentrations are frequently below those needed to exert therapeutic effect. One reason for the wide range in serum concentrations with standard oral formulations is that these products usually exhibit first-order drug absorption, in which the rate of absorption from the gastrointestinal tract continually varies following a dose (from high to low) and is directly determined by the amount of drug remaining in the gastrointestinal tract. First-order absorption, therefore, results in changing absorption rates, wide swings in serum drug concentrations, a relatively short duration of action, and often, inconsistent drug effects over a dosage interval. One way to address the problems with standard oral products that have first-order absorption is to produce products that control drug release and absorption. A large number of controlled-release oral products are now on the market and use a variety of technologies. The ideal controlled-release formulation would result in zero-order drug absorption, in which the rate of drug absorption from the gastrointestinal tract would be constant and not determined by the amount of drug in the gastrointestinal tract. Zero-order absorption, therefore, results in an unchanging absorption rate, consistent serum levels, a longer duration of action, and more steady drug effect. Zero-order absorption is particularly preferable in situations that require a consistent, long-term therapeutic effect, e.g., in patients with hypertension, asthma, or arrhythmias. Of all the controlled-release preparations on the market, however, very few exhibit zero-order absorption; most can be categorized somewhere between first- and zero-order kinetics. An advanced-technology tablet has been invented to produce zero-order drug absorption for prazosin and nifedipine.(ABSTRACT TRUNCATED AT 400 WORDS)
决定药物效应的因素包括药代动力学因素（由药物剂量、吸收、分布和排泄所决定的药物血清浓度）和药效学因素（药物效应的强度）。大多数药物效应评估聚焦于治疗范围，即血清浓度低于此范围不太可能产生治疗效果，高于此范围则可能出现毒性作用。许多治疗方案的目标是将血清药物浓度维持在治疗范围内。对于许多传统口服剂型而言，将药物浓度维持在治疗范围内可能很困难。在服用标准片剂、胶囊或液体后不久，血清中会观察到明显的峰值水平。在给药间隔结束时，血清浓度常常低于发挥治疗作用所需的浓度。标准口服制剂血清浓度波动范围大的一个原因是，这些产品通常呈现一级药物吸收，即胃肠道的吸收速率随剂量不断变化（从高到低），且直接由胃肠道中剩余的药量决定。因此，一级吸收导致吸收速率变化、血清药物浓度大幅波动、作用持续时间相对较短，并且在给药间隔内药物效应常常不一致。解决具有一级吸收的标准口服产品问题的一种方法是生产能控制药物释放和吸收的产品。现在市场上有大量控释口服产品，并采用了多种技术。理想的控释制剂会实现零级药物吸收，即胃肠道的药物吸收速率将是恒定的，且不受胃肠道中药物量的影响。因此，零级吸收导致吸收速率不变、血清水平一致、作用持续时间更长以及药物效应更稳定。在需要持续、长期治疗效果的情况下，如高血压、哮喘或心律失常患者，零级吸收尤为可取。然而，在市场上所有的控释制剂中，很少有呈现零级吸收的；大多数可归类于一级动力学和零级动力学之间的某个类型。已经发明了一种先进技术片剂，可实现哌唑嗪和硝苯地平的零级药物吸收。（摘要截取自400字）
