Clearance rate tests

It may be important to determine the degree of plasma protein and red blood cell binding of the test substance calculation of blood clearance rates using plasma or serum concentrations of the substance that have not been adjusted for the degree of binding may under or over-estimate the true rate of clearance of the test substance from the blood. This is usually done through experiments in vitro. 

Singh et al. (2006) investigated the tissue biodistribution and blood clearance rates of SWNTs in mice. Three different types of SWNTs were tested functionalized, water-soluble, and mIn-labeledDTPA-SWNT. All types exhibited a blood circulation... 

Nefazodone substantially decreases the clearance rate for triazolam, which results in a 400% increase in triazolam s serum levels (131). Erythromycin can also interfere with the metabolism of triazolam, resulting in decreased clearance and increased plasma levels, possibly causing toxicity. Troleandomycin and other macrolide antibiotics, such as clarithromycin, flurithromycin, josamycin, midecamycin, or roxithromycin, also may inhibit triazolam s metabolism (132). The coadministration of itraconazoie and triazolam can produce a marked elevation of triazolam plasma levels associated with statistically significant impairment of psychomotor tests and a prolongation of other effects (e.g., amnesia, lethargy, and confusion) for hours after awakening ( 133). 

In contrast with opiates and cocaine, an important number of cases were observed where urine tested positive for cannabinoids, whereas hair remained neg-ative. 2 This could be explained by an inadequate sensitivity of the hair assay or by the slow clearance rate of the cannabinoids in people taking cannabis for the first time. 

Renal function is an indication of the physiological state of the kidney glomerular filtration rate (GFR) describes the flow rate of Altered fluid through the kidney, while creatinine clearance rate (Ccr) is the volume of blood plasma that is cleared of creatinine per unit time, and is a useful measure for approximating the GFR. Most clinical tests use the plasma concentrations of the waste substances of creatinine and urea, as well as electrolytes, to determine renal function. The nephron is the functional unit of the kidney (Figure 10.1) it consists of two parts ... 

Extracellular clearance rate Prolonged (300-fold) (23, 36, 38) Not tested Prolonged (sixfold) (25)... 

To accelerate the procedure for bioconcentration tests, some investigators (8, 82, 83y 94) express bioconcentration factor as the ratio of the uptake rate constant to the clearance rate constant k2 in fish. In a flowing-water system, Needly et al. 83) found that the log(BCF) of some stable organic compounds determined from the kinetic rate constants in rainbow-trout muscle can be related to log The regression equation between the observed BCF and the calculated Aow values is... 

The route and frequency of administration should be as close as possible to that proposed for clinical use. Consideration should be given to pharmacokinetics and bioavailability of the product in the species being used, and the volume which can be safely and humanely administered to the test animals. For example, the frequency of administration in laboratory animals may be increased compared to the proposed schedule for the human clinical studies in order to compensate for faster clearance rates or low solubility of the active ingredient. In these cases, the level of exposure of the test emimal relative to the clinical exposure should be defined. Consideration should also be given to the effects of volume, concentration, formulation, and site of administration. The use of routes of administration other than those used clinically may be... 

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