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Clints

JH Clint, IR CoUins, JA WiUiams, BH Robinson, TF Towey, P Cajean, A Khan-Lodhi. Faraday Discnss 95 219-233, 1993. [Pg.502]

Fig. 3 Human liver microsome apparent intrinsic clearance (Clint,app) vs clogD. Open squares and filled triangles represent two different chemical series (series A and B, respectively)... Fig. 3 Human liver microsome apparent intrinsic clearance (Clint,app) vs clogD. Open squares and filled triangles represent two different chemical series (series A and B, respectively)...
Fig. 5 Pie charts for the two chemical series, colored by binned HLM Clint, free (white - low grey - moderate black - high) and arranged by binned clogD. Series A (bottom), series B (top)... Fig. 5 Pie charts for the two chemical series, colored by binned HLM Clint, free (white - low grey - moderate black - high) and arranged by binned clogD. Series A (bottom), series B (top)...
Equation (1) was derived assuming no protein binding, whereas, in fact, CLint should be defined in terms of the maximum ability of the organ to remove unbound drug because only unbound drug can bind to enzymes and excretory molecules. By including the unbound fraction of drug in Eq. (4) one obtains... [Pg.141]

However, for many drugs, blood flow is significantly greater than the intrinsic organ clearance (Q fu CLint) and then Eq. (5) reduces to... [Pg.141]

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... [Pg.141]

Q >fu CLint, then Eq. (7) simply says that the first-pass bioavailability is approximately 1 (i.e., little or no drug is eliminated in a first pass), and changes in binding, blood flow, and intrinsic clearance are not expected to have any effect on F. [Pg.141]

The species differences in biotransformation pathways, rates of elimination, and intrinsic hepatic clearance of esfenvalerate and deltamethrin using rat and human liver microsomes were examined [33]. Esfenvalerate was eliminated primarily via NADPH-dependent oxidative metabolism in both rat and human liver microsomes. The CLint of esfenvalerate was estimated to be threefold greater in rodents than in humans on a per kg body weight basis. Deltamethrin was also eliminated primarily via NADPH-dependent oxidative metabolism in rat liver microsomes however, in human liver microsomes, deltamethrin was eliminated almost entirely via... [Pg.123]

NADPH-independent hydrolytic metabolism. The CLint for deltamethrin was estimated to be twice as rapid in humans as in rats on a per kg body weight basis. Metabolism by purified rat and human CESs was used to examine further the species differences in hydrolysis of deltamethrin and esfenvalerate. Results of CES metabolism revealed that hCEl was markedly more active toward deltamethrin than the Class I rat CESs, hydrolase A and B, and the Class II human CES, hCE2 however, hydrolase A metabolized esfenvalerate twice as fast as hCEl, whereas hydrolase B and hCEl hydrolyzed esfenvalerate at equal rates. These studies demonstrated a significant species difference in the in vitro pathways of biotransformation of deltamethrin in rat and human liver microsomes, which was due in part to differences in the intrinsic activities of rat and human CESs. [Pg.124]

Since Clint is proportional to Ess and because Clint is inversely proportional to AUC, the following relationship is valid ... [Pg.220]

R. Aveyard, B.P. Binks, and J.H. Clint Emulsions Stabilized Solely by Colloidal Particles. Adv. CoUoid Interface Sci. 100-102, 503 (2003). [Pg.142]


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See also in sourсe #XX -- [ Pg.123 , Pg.124 , Pg.125 , Pg.126 , Pg.127 , Pg.128 , Pg.129 , Pg.130 , Pg.131 , Pg.132 , Pg.133 ]




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