Elimination, biphasic

Hypochlorite readily chlorinates phenols to mono-, di-, and tri-substituted compounds (163). In wastewater treatment chlotophenols ate degraded by excess hypochlorite to eliminate off-flavor (164). Hypochlorite converts btomoben2ene to cb1oroben2ene in a biphasic system at pH 7.5—9 using phase-transfer catalysts (165). 

Industrial environments expose individuals to a plethora of airborne chemical compounds in the form of vapors, aerosols, or biphasic mixtures of both. These atmospheric contaminants primarily interface with two body surfaces the respiratory tract and the skin. Between these two routes of systemic exposure to airborne chemicals (inhalation and transdermal absorption) the respiratory tract has the larger surface area and a much greater percentage of this surface exposed to the ambient environment. Or dinary work clothing generally restricts skin exposures to the arms, neck, and head, and special protective clothing ensembles further limit or totally eliminate skin exposures, but breathing exposes much of the airway to contaminants. 

Working with rats, Lntz et al. (1977) compared the rates of loss from blood of 4,-CB (rapidly metabolized) with that of 2,2, 4,4, 5 -HCB (slowly metabolized). Both showed biphasic elimination, with the former disappearing much more rapidly than the latter. Estimations were made of the rates of hepatic metabolism in vitro, which were then incorporated into toxicokinetic models to predict rates of loss. The predictions for HCB were very close to actual rates of loss for the entire period of... 

In a study of metabolism of 14C-flocoumafen by the Japanese quail (Huckle et al. 1989), biotransformation was extensive and rapid, with eight metabolites detected in excreta. The elimination of radioactivity from the liver of Japanese quail was biphasic (Figure 11.2). After an initial period of rapid elimination, there followed a... 

To eliminate the need to recover the product by distillation, researchers are now looking at thermomorphic solvent mixtures. A thermomorphic system is characterized by solvent pairs that reversibly change from being biphasic to monophasic as a function of temperature. Many solvent pairs exhibit varying miscibility as a function of temperature. For example, methanol/cyclohexane and n-butanol/water are immiscible at ambient temperature, but have consolute temperatures (temperatures at which they become miscible) of 125°C and 49°C, respectively (3). 

There was a significant negative correlation between (log) admission urinary PCP level and self-reported time since last PCP use (r= -0.53, p<0.001). Visual inspection of a graph of these two variables suggested a possible biphasic elimination curve, with the initial phase having a half-life of 5 to 7 days, and the later phase a half-life of about 30 days. However, formal curve fitting of these data to standard pharmacokinetic models (using BMDP... 

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). 

Toxicokinetics of PCBs in rodents were altered when administered in mixtures (de Jongh et al. 1992). PCBs 153, 156, and 169 produced biphasic elimination patterns in mice when administered in combinations, but single-phase elimination when administered alone. Elimination of all PCBs was more rapid after coadministration. Mixtures of PCBs 153 and 156 raised EROD activity and lengthened retention of each congener in liver however, a mixture of PCB 153 and 169 lowered EROD activity (de Jongh et al. 1992). Selected PCBs of low acute toxicity may increase the toxicity of compounds such as 2,3,7,8-TCDD (Bimbaum et al. 1985). Thus, PCB 153 or 157 at sublethal dosages (20 to 80 mg/kg BW) did not produce cleft palate deformities in mouse embryos. But a mixture of PCB 157 and 2,3,7,8-TCDD produced a tenfold increase in the incidence of palate deformities that were expected of 2,3,7,8-TCDD alone palate deformities did not increase with a mixture of PCB 153 and 2,3,7,8-TCDD. The widespread environmental occurrence of PCB-PCDD and PCB-PCDF combinations suggests a need for further evaluation of the mechanism of this interaction (Bimbaum et al. 1985). 

Peak plasma levels are reached about 1.5 h after oral ingestion, the maximum concentrations being in the order of 2 - 3 ng equivalents/ml (parent drug + metabolites) for an oral 1 mg dose. The elimination from the plasma is biphasic and proceeds with mean half-lives of 6 h (a-phase) and 50 h ((3-phase). Similar elimination half-lives are obtained from the urinary excretion. The cumulative renal excretion is practically the same after oral and intravenous administration and amounts to 6 - 7 % of the radioactivity dosed. The main portion of the dose, either oral or intravenous, is eliminated by the biliary route into the faeces. The kinetics of bromocriptine has been demonstrated to be linear in the oral dose range from 2.5 to 7.5 mg. 

Recently, the fluorous biphasic separation technique has been enriched with two new developments, both of which were demonstrated in hydrogenation. The need for a fluorous solvent can be eliminated by using fluorous silica as a fluorous catalyst scavenger. In liquid-liquid biphasic systems, reversible expan-... 

The consequence of incomplete phase separation in a biphasic catalysed reaction results in contamination of the product phase by some of the catalyst immobilization solvent, as well as the catalyst. In the worst possible case, a distillation process is still required to purify the product. In addition, with some of the catalyst lost from the immobilization phase (the catalyst is often expensive and toxic) the system is less active when a second batch of the substrate is introduced. The best way to minimize (or ideally eliminate) catalyst loss is to design a catalyst that is considerably more soluble in the immobilization phase compared to the product phase. This is usually done by attaching groups to the catalyst that provide the desired solubility properties for the immobilization solvent and many examples of these modified ligands are given in the following chapters. 

Transfer of the aquatic animals, after absorption of the cyclodiene, to insecticide-free water showed variations in elimination pattern related with the chemical as well as its concentration in the body. It follows a somewhat biphasic response, there is initial rapid elimination of high concentration followed by a slow elimination at lower body concentrations (Fig. 3)(21,22, 23). Xenopus, even at low body levels of cis-chlordane, eliminate it at slightly faster rate than fish. Photo-cis-chlordane seems to be eliminated at a faster rate than cis-chlordane by both goldfish and bluegill (Table 2). The elimination of photo-cis-chlordane by goldfish and bluegill and of photodieldrin by blue-gill shows a biphasic response (Fig. 3). 

The preparation of novel phase transfer catalysts and their application in solving synthetic problems are well documented(l). Compounds such as quaternary ammonium and phosphonium salts, phosphoramides, crown ethers, cryptands, and open-chain polyethers promote a variety of anionic reactions. These include alkylations(2), carbene reactions (3), ylide reactions(4), epoxidations(S), polymerizations(6), reductions(7), oxidations(8), eliminations(9), and displacement reactions(10) to name only a few. The unique activity of a particular catalyst rests in its ability to transport the ion across a phase boundary. This boundary is normally one which separates two immiscible liquids in a biphasic liquid-liquid reaction system. 

Chloroform in humans tends to be eliminated in a biphasic manner. After ingesting 500 mg of chloroform orally, an initial (a) half-life in the blood of 9-21 minutes was reported, with the second (P) half-life ranging from 86 to 96 hoirrs. 

It is often useful to keep some of the reactants or the products in separate phases (principle of chemical protection by phase separation [53]). For instance, when the reaction is inhibited by its own substrate having the latter in an other phase than the one in which the catalyst is dissolved helps to eliminate long induction periods or complete stop of the reaction. An example is the biphasic hydrogenation of aldehydes with the water-soluble... 

In animals, absorption of 3,3 -dichlorobenzidine from the gastrointestinal tract is rapid. Following a dose of 40 mg/kg, the plasma level of imchanged 3,3 -dichlorobenzidine attained a peak concentration of 1.25 g/mL at 4 hours in Sprague Dawley rats. Further, about 90% of the administered radioactivity was excreted in feces (via bile) and urine within 72 hours largely as metabolites, indicating a high bioavailability, typical of primary aiylamines. The elimination is biphasic, with half-lives of 6 hours and 14 hours in plasma for the rapid and slow phases, respectively (Hsu and Sikka 1982). 

The disappearance of tritiated vindesine from the blood of rats has been reported to be biphasic, with half-life estimates of 15 min (distribution) and 10 hr (elimination) (59) it is likely that the prolonged elimination phase represents a hybrid between the second elimination phase described above for vincristine and the prolonged third phase evident on inspection of log concentration-time plots for vincristine in the rat. Biliary excretion contributes heavily to the elimination of vindesine in the rat. The bioavailability of vindesine in the rat appears to be very poor. The distribution of vincristine to different tissues in the mouse has been correlated with the estimated concentration of tubulin in the tissues (40). Tubulin concentration was measured by the capacity of a tissue to bind colchicine (40) comparable relationships between tissue concentrations of vincristine and colchicine binding capacity were observed for the dog and the monkey, but it should be emphasized that the correlations were based on the assumption that tissue tubulin content is closely similar in the mouse, dog, and monkey. 

Elimination of P743 from the intravascular compartment is best described by a biphasic model in rabbits (Fig. 11). 

In calves and cows at high dose levels (100 SDM mg/kg), a biphasic elimination SDM plasma concentration-time curve was observed with a steady state plasma SCH2OH concentration resulting from the capacity limited hydroxylation of SDM into the latter. The drug concentrations in the milk reflected those in plasma. 

Laying-hens eliminate sulfadimidine rapidly by metabolic pathways including hydroxylation and acetylation. Following intravenous SDM administration, a biphasic elimination-time curve was noticed 10.2 + 3.3 H). Figure 8 shows the plasma disposition of SDM and its metabolites following an oral SDM bolus administration once daily of 100 mg/kg to a chicken. The percentage of N -SDM in plasma is the highest (Table I). Within 3 days of termination of the SDM therapy, plasma concentrations of SDM and its metabolites falls rapidly below the detection limit of the HPLC method (0.02 /ig/ml). 

As shown above, the plasma drug concentration usually exhibits a biphasic rise and fall that are characteristic of all two-step series first-order processes. When k is zero, there will only be first-order absorption without any elimination, and when k > k, drug absorption will be virtually instantaneous, followed by first-order elimination. 

Excretion - The elimination of treprostinil is biphasic, with a terminal half-life of approximately 4 hours. Approximately 79% of an administered dose is excreted in the urine as unchanged drug (4%) and as the identified metabolites (64%). Approximately 13% of a dose is excreted in the feces. 

Excretion - Following discontinuation of chronic oral therapy, amiodarone has a biphasic elimination with an initial one-half reduction of plasma levels after 2.5 to 107 days. A much slower terminal plasma elimination phase shows a half-life of the parent compound of approximately 53 days. For the metabolite, mean plasma elimination half-life was approximately 61 days. Antiarrhythmic effects persist for weeks or months after the drug is discontinued. 

Metabolism/Excretion-Trazodone is extensively metabolized in the liver and is a CYP3A4 substrate. Elimination is biphasic, with a half-life of 3 to 6 hours and 5 to 9 hours, respectively, and is unaffected by food. 

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