Terminal phase

Fig. 3.6. (a) The copper-nickel diagram is a good deal simpler than the lead-tin one, largely because copper and nickel are completely soluble in one another in the solid state. (b) The copper-zinc diagram is much more involved than the lead-tin one, largely because there are extra (intermediate) phases in between the end (terminal] phases. However, it is still an assembly of single-phase and two-phase fields. 

All parameters of interest with respect to fragmentation will be discussed. The extent of damage or injury caused by these fragments is, however, not covered in this volume. (Parameters of the terminal phase include first, fragment density and velocity at impact, and second, resistance of people and structures to fragments.)... 

In many systems, both single-phase and polyphase behaviors are found in different composition ranges. Intermediate, as well as terminal, phases often have been found to have quite wide ranges of composition. Examples are the broad Zintl phases found in several of the binary lithium systems studied by Wen [29]. 

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. 

Cf = steady-state drug concentration in tissue i Cp = steady-state drug concentration in plasma C° = terminal phase y-axis intercept from tissue drug concentrationtime plot... 

In rats, excretion of lead was biphasic following intravenous administration, with half-lives of 21 hours for the fast phase and 280 hours for the slow phase (Morgan et al. 1977). Dogs excreted lead in three phases, with half-lives of 12, 184, and 4,951 days (Lloyd et al. 1975). The half-life of the terminal phase of a biphasic elimination curve for mice was 110 days (Keller and Doherty 1980a). 

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. 

Methods for calculating volume of distribution (VD) can be influenced by renal disease. Of the commonly used terms (i.e., volumes of central compartment, terminal phase, and distribution at steady state [ Vss]), Vss is the most appropriate for comparing patients with renal insufficiency versus those with normal renal function because Vss is independent of drug elimination. 

Figure 12.2 Schematic representation of the CHS and STS reactions. The reaction pathway highlights the initiation, elongation, and termination phases of the polyketide extension reaction.

Extreme cases of solid solubility are shown in Fig. 2.11. In particular notice the system Au-Si for which, owing to a negligible solubility in the solid state, the terminal phases are practically coincident with the pure elements. 

In Fig. 2.19, on the contrary, we observe that intermediate solid phases with a variable composition are formed (non-stoichiometric phases). In the diagrams shown here we see therefore examples both of terminal and intermediate phases. (For instance, the Hf-Ru diagram shows the terminal solid solutions of Ru in a and (3Hf and of Hf in Ru and the intermediate compound containing about 50 at.% Ru). These phases are characterized by homogeneity ranges (solid solubility ranges), which, in the case of the terminal phases, include the pure components and which, generally, have a variable temperature-dependent extension. 

The mean SD volume of distribution of micafungin at terminal phase was 0.39 0.11 L/kg body weight when determined in adult patients with esophageal candidiasis at the dose range of 50 to 150 mg. 

Nevirapine has been shown to be an inducer of hepatic cytochrome P450 metabolic enzymes 3A4 and 2B6. The pharmacokinetics of autoinduction are characterized by an approximately 1.5- to 2-fold increase in the apparent oral clearance of nevirapine as treatment continues from a single dose to 2 to 4 weeks of dosing with 200 to 400 mg/day. Auto-induction also results in a corresponding decrease in the terminal phase half-life of nevirapine in plasma from approximately 45 hours (single dose) to approximately 25 to 30 hours following multiple dosing with 200 to 400 mg/day. 

Zanamivir (2) is a potent competitive inhibitor of viral neuraminidase glycoprotein, which is essential in the infective cycle of both influenza A and B viruses. It inhibits a wide range of influenza A and B types in vitro as well as in vivo. The concentrations of inhibiting in vitro plaque formation of influenza A and B virus by 50% in Madin-Darby canine kidney (MDCK) cells were 0.004-0.014 p.mol/L in laboratory-passaged strains, and 0.002-16 p.mol/L in assays of clinical isolates. Due to its low bioavailability, it is delivered by inhalation via the Diskhaler , 10 mg twice daily, or intranasally 2-4 times daily for 5 days. After an intravenous dose of 1 -16 mg, the median elimination half-life was ti/2 = 7 h, the volume of distribution at steady state was Vdss = 16 L, and 90% of the dose was excreted unchanged in the urine. After intranasal and inhaled (dry powder) administration, maximum serum concentrations occurred within 2h and the terminal phase half-lives were 3.4 and 2.9 h, respectively. The bioavailabilities were 10 and 25%, respectively, and 20% after inhalation of zanamivir (2) by nebulizer. 

Studies on human volunteers given DMHP Intravenously Indicated a half-life of the terminal phase of [1 C]DMHP elimination of 39 h ... 

For a two-compartment model C=0 and the equation is bi-exponential. The exponents o, jSand y are related to the intercompartmental transfer rate constants by complex formulae. They are related to the half-lives for each of the distribution and terminal phases by the relationship ... 

Despite the lack of anatomical identity the concept of apparent volume of distribution does have value. It can be considered as the volume from which a drug must be cleared. Thus, for a drug with a large VD, the plasma concentration during the terminal phase will decline slower than one with a smaller VDand similar clearance. This can be seen by rearranging the equation above ... 

The half-life of mercury is long, but there are two phases, the first being around 2 days, then the terminal phase, which is around 20 days. However, the half-life will depend on the form of mercury. Thus, methyl mercury has a half-life of about 70 days, whereas for inorganic mercury, this is about 40 days. 

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