Generalized elimination clearance

Renwick (1993) examined the relative magnitude of toxicokinetic and toxicodynamic variations between species in detail and found that toxicokinetic differences were generally greater than toxicodynamic differences. In order to allow for separate evaluations of differences in toxicokinetics and toxicodynamics, he proposed that the default interspecies UF of 10 should, by default, be subdivided into a sub-factor of 4 for toxicokinetics and a sub-factor of 2.5 for toxicodynamics. The suggested factor of 4 for differences in toxicokinetics was largely based on the extent of absorption and the rate of elimination or clearance in different experimental animals. The suggested... 

A broad and vigorons T cell response generally accompanies elimination of HBV as well as HCV infection. By contrast, patients with chronic hepatitis B or C tend to have late, transient, or narrow T cell responses. In a long-term follow-up of HBV-infected patients receiving HPC transplants from HBV-immune individuals, 20 of 31 recipients cleared their HBV infection (Hui et al. 2005). In principle, these results encourage the development of adoptive T cell transfer strategies for the treatment of chronic viral hepatitis. However, it is still controversial whether induction of an efficient T cell response is the cause or the consequence of viral clearance. Furthermore, T cell responses do not only contribute to virus control but also to disease pathology (Rehermann and Nascimbeni 2005). 

Despite a relatively fast clearance of chloroform from the body, toxic effects may develop in exposed individuals. No method is commonly practiced to enhance the elimination of the absorbed dose of chloroform. Although there is evidence that ethanol pretreatment of rats can increase the in vitro metabolism of chloroform (Sato et al. 1981), such treatment would not be recommended (Kutob and Plaa 1962) because it would increase the toxicity of chloroform and it is a very poor practice generally. 

The effect of age on the renal elimination of some drugs is shown in Table 2. In general, the dose can be guided by the estimated or measured creatinine clearance. This should be performed in particular... 

The use of inhalational anesthetics is generally reserved for maintenance of anesthesia. The development of an anesthetic concentration in the brain occurs more slowly with inhalational anesthetics than with IV drugs. Once an anesthetic level has been achieved, however, it is easily adjusted by controlling the rate or concentration of gas delivery from the anesthesia machine. The rate of recovery from a lengthy procedure in which inhalational agents are used is reasonably rapid, since inhalational anesthetics are eliminated by the lungs and do not depend on a slow rate of metabolism for their tissue clearance. Thus, inhalational drugs meet the requirement for a relatively prompt return of the patient s psychomotor competence. 

In general, a drug is eliminated either unchanged through excretion in the urine and/ or bile or by metabolic conversion into more polar metabohte(s) that can be readily excreted in urine and/or bile. Therefore, total body clearance is a sum of all clearances by various mechanisms and can be expressed mathematically as... 

E. Nakashima and L. Z. Benet. General treatment of mean residence time, clearance, and volume parameters in linear mammillary models with elimination from any compartment. J. Pharm. Biopharm. 16 475-492, 1988. 

---