Ratios extraction

Figure 20 shows values of the channel enthalpy extraction ratio for a number of channels. Enthalpy extraction (111) equal to that required by a proposed demonstration plant (112) has been achieved. Channels have performed generally in accordance with predictions. 

Example 6 Slurry Sampling by Rotary Traverse of Gravity Flow Increment volume, quantity of slurry extracted hy one cutter rotation, is S from hulk slurry flow B expressed in voliime-per-imit time. R is cutter rotation per minute. D is cutter angle opening, with D/360 extraction ratio for continuous cutter rotation. 

Expt no. HPO amount (%) Conversion (%) Average particle size (/Lirn) Residual PVAc in porous film i%r Extraction ratio vs. total PVAc (%)... 

Since one proton separation will hardly occur at pH 2.2, extraction ratios of Fe " with compounds 1-7 are quite low. Yet compound 8, which carries oxime groups, was able to extract a considerable amount of Fe- at pH 2.2. 

As a rule of thumb, 50 to 55 percent of coal can be extracted using continuous mining. To improve this extraction ratio, a pillar-recovery process usually is applied when mining reaches the end of the panel and the direction of the mining is reversed. The continuous miner mines into the pillars, recovering as much coal as possible, as the roof is allowed to systematically collapse. Usually this can increase the extraction ratio by up to 5 percent. 

To further investigate the role of the liver in brevetoxin metabolism, PbTx-3 was studied in the isolated perfused rat liver model (27, 28). Radiolabeled PbTx-3 was added to the reservoir of a recirculating system and allowed to mix thoroughly with the perfusate. Steady-state conditions were reached within 20 min. At steady-state, 55-65% of the delivered PbTx-3 was metabolized and/or extracted by the liver 26% remained in the effluent perfusate. Under a constant liver perfusion rate of 4 ml/min, the measured clearance rate was 0.11 ml/min/g liver. The calculated extraction ratio of 0.55 was in excellent agreement with the in vivo data. Radioactivity in the bile accounted for 7% of the total radiolabel perfused through the liver. PbTx-3 was metabolized and eliminated into bile as parent toxin plus four more-polar metabolites (Figure 3). Preliminary results of samples stained with 4-(p-nitrobenzyl)-pyridine (29) indicated the most polar metabolite was an epoxide. 

Data from both in vivo and in vitro systems showed PbTx-3 to have an intermediate extraction ratio, indicating in vivo clearance of PbTx-3 was equally dependent upon liver blood flow and the activity of toxin-metabolizing enzymes. Studies on the effects of varying flow rates and metabolism on the total body clearance of PbTx-3 are planned. Finally, comparison of in vivo metabolism data to those derived from in vitro metabolism in isolated perfused livers and isolated hepatocytes suggested that in vitro systems accurately reflect in vivo metabolic processes and can be used to predict the toxicokinetic parameters of PbTx-3. 

Table 1 Drugs Suspected to Have High Hepatic Extraction Ratios...

This indicates that the first-pass availability is a function of organ flow, protein binding, and intrinisic clearance of the organ. When fu CLint Q (i.e., when we have relatively large extraction ratios), the first-pass bioavailability is equal to... 

Under this circumstance, the first-pass bioavailability is inversely proportional to the unbound fraction, and changes in the binding are expected to have a significant effect. It is also clear that changes in both the blood flow and the intrinsic clearance of the first-pass organ may have a significant effect when the extraction ratio is high (fu CL n Q). On the other hand, if... 

The expression of metabolic enzymes in the enterocyte can lead to a profound gut wall first-pass extraction ratio for substrate drugs. In addition, efflux transporters can slow the passage of drugs across the enterocyte in a cycling fashion. This allows the metabolic enzymes several opportunities to metabolize their substrates, and in this way a low expression level of an enzyme can exhibit a significant extraction. 

The expression of a significant gut wall first-pass extraction ratio has several implications for affected drugs. First, oral bioavailability is lower than would be expected from the extent of absorption and the hepatic first-pass extraction. Second, the variability in expression of gut wall metabolic enzymes and transporters can lead to significant variability in gut wall first-pass extraction and thus oral bioavailability. Finally, the site of expression of these enzymes and transporters (i.e., the villus tip) brings them into contact with potentially co-administered drugs or dietary constituents, which could be inhibitors or inducers. Thus, there is the potential for drug-drug interactions at the level of the gut wall. 

The extraction ratio is dependent upon the amounts of drug entering (Cj) and exiting (CD) the organ ... 

The Vo2 Do2 ratio (oxygen extraction ratio) can be used to assess adequacy of perfusion and metabolic response. Patients who are able to increase Vo2 when Do2 is increased are more likely to survive. However, low Vo2 and 02 extraction ratio values are indicative of poor 02 utilization and lead to greater mortality. 

T or si Free fraction of highly plasma protein-bound drugs si Clearance and T t1/2 for some oxidatively metabolized drugs si Clearance and T t1/2 for drugs with high hepatic extraction ratios si Clearance and T t 2 for renally eliminated drugs and active metabolites... 

Lau, Y.Y. et al. 2002. The use of in vitro metabolic stability for rapid selection of compounds in early discovery based on their expected hepatic extraction ratios. Pharm. Res. 19 1606. 

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