Distributive phase

A composite material (1) is a material consisting of two or more physically and/or chemically distinct, suitably arranged or distributed phases, generally having characteristics different from those of any components in isolation. Usually one component acts as a matrix in which the reinforcing phase is distributed. When the continuous phase or matrix is a metal, the composite is a metal-matrix composite (MMC). The reinforcement can be in the form of particles, whiskers, short fibers, or continuous fibers (see Composite materials). 

Half-life is the time taken to decrease the concentration of a drug to one-half its original value. There may be several phases in the elimination, and the most common is the so-called beta-phase. Alpha-phase is a distribution phase and gamma-phase is the terminal phase when the drug is finally leaving the tissues. 

The subscripts m, L, S, and G will represent the local two-phase mixture, liquid phase, solid phase and gas phase, respectively. The definitions below are given in terms of solid-liquid (S-L) mixtures, where the solid is the more dense distributed phase and the liquid the less dense continuous phase. The same definitions can be applied to gas-liquid (G-L) flows if the subscript S is replaced by L (the more dense phase) and the L by G (the less dense phase). The symbol

volume fraction of the more dense phase, and s is the volume fraction of the less dense phase (obviously (p = 1 — e). An important distinction is made between ([Pg.444]

Pharmacokinetic studies indicate the product displays two-compartment behaviour, with a distribution phase (half-life 2-5 min) and a terminal phase (half-life 70-80 min). Development of antibodies to the product significantly impacts upon clearance rates. 

Particle size distribution Phase volume fraction Lamellar structure Polymorphism... 

Mezlocillin, piperacillin, and ticarcillin are parenteral antibiotics formulated as sodium salts, so prescribers must consider the sodium content of these antibiotics when administering them to patients with congestive heart failure. During their distribution phase, antipseudomonal penicillins achieve orfly low concentrations in the cerebrospinal fluid. Consequently, antipseudomonal penicillins are not among the drugs of first choice for meningitis therapy. 

The pharmacokinetic properties of aztreonam are similar to those of the parenteral cephalosporins (Table 45.2). Aztreonam is not bioavailable after oral administration. During its distribution phase, the drug can achieve therapeutic concentrations in cerebrospinal fluid in the presence of inflamed meninges. Consequently, aztreonam is an alternative antibiotic to the cephalosporins for the therapy of meningitis caused by gram-negative bacilli. 

The plasma half-life of dacarbazine is biphasic, with a distribution phase of 19 minutes and an elimination phase of 5 hours. The drug is not appreciably protein bound, and it does not enter the central nervous system... 

Methotrexate is well absorbed orally and at usual dosages is 50% bound to plasma proteins. The plasma decay that follows an intravenous injection is triphasic, with a distribution phase, an initial elimination phase, and a prolonged elimination phase. The last phase is thought to reflect slow release of methotrexate from tissues. The major routes of drug excretion are glomerular filtration andl active renal tubular secretion. 

Cisplatin shows biphasic plasma decay with a distribution phase half-life of 25 to 49 minutes and an elimination half-life of 2 to 4 days. More than 90% of the drug is bound to plasma proteins, and binding may approach 100% during prolonged infusion. Cisplatin does not cross the blood-brain barrier. Excretion is predominantly renal and is incomplete. 

Knowing the differential pharmacokinetics for a class of drugs allows the clinician to choose specific members to either achieve a faster onset or a delayed offset of action (13, 14, 17, 18). For example, lorazepam is rapidly absorbed from the gastrointestinal tract into the systemic circulation and from there distributed into the brain. In contrast, oxazepam, the most polar BZD, is slowly absorbed from the gastrointestinal tract. Even after oxazepam is in the systemic circulation, it slowly enters tissue compartments, including the brain, during the distribution phase. Unlike lorazepam, oxazepam is not available in either the intramuscular or intravenous formulations. Thus, lorazepam would be preferable to achieve acute control of alcohol withdrawal (e.g., delirium tremens), whereas oxazepam would better stabilize a dependency-prone patient on sedative-hypnotics, because it does not cause the euphoria seen with the more rapidly absorbed members of this class. 

The amide local anesthetics are widely distributed after intravenous bolus administration. There is also evidence that sequestration can occur in lipophilic storage sites (eg, fat). After an initial rapid distribution phase, which consists of uptake into highly perfused organs such as the brain, liver, kidney, and heart, a slower distribution phase occurs with uptake into moderately well-perfused tissues, such as muscle and the gastrointestinal tract. As a result of the extremely short plasma half-lives of the ester type agents, their tissue distribution has not been extensively studied. 

Aminoglycosides are absorbed very poorly from the intact gastrointestinal tract almost the entire oral dose is excreted in feces after oral administration. However, the drugs may be absorbed if ulcerations are present. After intramuscular injection, aminoglycosides are well absorbed, giving peak concentrations in blood within 30-90 minutes. Aminoglycosides are usually administered intravenously as a 30- to 60-minute infusion after a brief distribution phase, this results in serum concentrations that are identical with those following intramuscular injection. 

The circulatory system of fish is also unique structurally and functionally. Structurally, the membranous nature of the vasculature makes for a friable high-capacitance system under low pressure. Low blood flows result in somewhat longer distributional phases for many drugs. Processes such as heart rate and stroke volume that influence drug distribution are themselves influenced by external factors such as temperature and stress. In addition, total plasma protein content differs in fish as compared to mammals. Total plasma protein in the trout and flounder is approximately one-half that of mammals such as dogs and cats. For many compounds protein binding is considerably lower in fish than their mammalian counterparts (19, 20). 

The balance over the lumped, or uniform, phase recognizes that there is only one source of the reacting species, namely the transfer from the distributed phase, whereas the chemical disappears by reaction and by washout ... 

A two-compartment open linear model has been described for the pharmacokinetic profile of cocaine after intravenous administration.14 The distribution phase after cocaine administration is rapid and the elimination half-life estimated as 31 to 82 min.14 Cone9 fitted data to a two-compartment model with bolus input and first-order elimination for the intravenous and smoked routes. For the intranasal route, data were fitted to a two-compartment model with first-order absorption and first-order elimination. The average elimination half-life (tx 2 3) was 244 min after intravenous administration, 272 min after smoked administration, and 299 min after intranasal administration. 

In some instances one of the phases is distributed and the other phase is lumped. In such a case the distributed phase will contribute its mass and/or heat-transfer term to the lumped phase through an integral as shown in the model of a bubbling fluidized bed in Chapter 4. 

A well known result states that the values of the discrete Fourier transform of a stationary random process are normally distributed complex variables when the length of the Fourier transform is large enough (compared to the decay rate of the noise correlation function) [Brillinger, 1981], This asymptotic normal behavior leads to a Rayleigh distributed magnitude and a uniformly distributed phase (see [McAulay and Malpass, 1980, Ephraim andMalah, 1984] and [Papoulis, 1991]). 

Figure 6.13 (a) Semilog plot of plasma concentration for (Cp) versus time representative of a two-compartment model. The curve can be broken down into an a or X i distribution phase and ft or k2 elimination phase, (b) Two-compartment model with transfer rate constants, Kn and K2, and elimination rate constant, Ke. ... 

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