By Ali S. Faqi (Auth.)
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Extra resources for A Comprehensive Guide to Toxicology in Preclinical Drug Development
4 Plasma concentration versus time curve after IV administration with a gray rectangle representing an estimate of the area under the curve between 2 and 4 hr. The height of the rectangle is approximately the average concentration between 2 and 4 hours and the width is 2 hours. The area of the rectangle is therefore ~250 mg/mL Â 2 hr ¼ 500 mg∙hr/mL. 36 3. PHARMACOKINETICS AND TOXICOKINETICS where Conc is the average concentration during a short duration of time, Dt is the time interval, and clearance is equivalent to the filter clearance rate.
2, a similar beaker is shown, but in this case a filter has been inserted in front of the pump. This filter removes some of the molecules as the fluid passes through. 1 where no filter was in place. , minutes or hours, will result in a lower concentration as the filter has reduced the amount of compound in the beaker. The filter in this example is analogous to the liver, which frequently removes a drug from circulation, and is a site of both drug excretion (via the bile) and metabolism. 2 A beaker that contains water which is continuously circulated and mixed by a pump.
10), Eq. 21) shows the relationship between clearance, volume of distribution, and the elimination rate constant, lz . 21) Considering Eq. 20), solving for lz and substituting into Eq. 22) Thus, t1/2 will increase as CL decreases or Vd increases (Vz in this case). 22) is written specifically to highlight that CL and Vd, two independent parameters, both control t1/2 which is a dependent parameter. 42 3. 2 L/hr . 5 hr. The example of SensiparÒ is not as clear [12,13]. 1 L/hr/ kg (~87% of hepatic blood flow; see the section ‘Practical Considerations’, section ‘Normalization of Clearance Values to Liver Blood Flow’).