Clearance rate

This concept becomes important in determining the effects of organ pathology on clearance and on the role of blood dow to individual organs in calculating clearance rate. 

Synthetic steroid with strong glucocorticoid-agonistic activity. Dexamethasone is over 10 times more potent than cortisol due to a higher binding affinity for glucocorticoid receptor and a decreased clearance rate of the compound. Due to its potency, dexamethasone is widely used in the clinics for the treatment of inflammatory diseases. 

Little is known regarding the pharmacokinetic properties of volatile nitrites in humans, particularly isobutyl nitrite and its primary metabolite, isobutyl alcohol. In rodents, after an intravenous infusion of isobutyl nitrite, blood concentrations peaked rapidly and then declined, with a half-life of 1.4 minutes and blood clearance rate of 2.9 L/min/kg (Kielbasa and Fung 2000). Approximately 98% of isobutyl nitrite is metabolized rapidly to isobutyl alcohol, concentrations of which also decline rapidly, with a half-life of 5.3 minutes. Bioavailability of inhaled isobutyl nitrite at a concentration of 300-900 ppm is estimated to be 43%. 

Figure 3). Except for the first two days following administration, the clearance of activity from the body followed apparent first order rate kinetics. The half-life for clearance, ti/2, was 17.4 dt 5.6 days. As previously indicated, it was assumed that the relatively large amount excreted during the first 2 days had not been absorbed therefore, these values were not used in calculating the clearance rate. 

Juliano, R. L., and Stamp, D. (1975). Effect of particle size and charge on the clearance rates of liposomes and liposome encapsulated drugs, Biochlm. Biophys. Res. Commun.. 63, 651-658. 

Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD. HlV-1 dynamics in vivo virion clearance rate, infected cell life-span, and viral generation time. Science 1996 271 1582-6. 

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. 

The study of the mechanism of urinary excretion of amylase and the amylase clearance has been the subject of many studies in recent years. Levitt et. al (79) studied the renal clearance of amylase in renal insufficiency, acute pancreatitis and macro-amylasemia. In acute pancreatitis, the kidney cleared amylase at a markedly increased rate. The ratio of the amylase clearance rate to the creatinine clearance rate (Cgm/Ccr) averaged 3 times normal early in the course of acute pancreatitis, and this elevation could persist after the serum amylase returned to normal. Comparison of an lase clearance to creatinine clearance was to minimize irrelevant changes due to variation in renal function. The increased clearance of amylase makes the urinary amylase a more sensitive indicator of pancreatitis. 

Polyphenols are not found free in the blood but are bound to plasma proteins. Albumin is the primary protein responsible for the bindings of several polyphenols and their metabolites (i.e., quercetin, kempferol, isorhamnetin), but no data are available for anthocyanins. However it is probable that anthocyanin derivatives also bind to albumin and the degree of that binding may affect the clearance rate and the delivery to tissues of these compounds as well. 

CBP Cromolyn-binding protein CCK Cholecystokinin CCR Creatinine clearance rate CD Cluster of differentiation (a system of nomenclature for sur ce molecules on cells of the immune system) cluster determinant CDl Cluster of differentiation 1 also known as MHC class I-like surfitce glycoprotein... 

Respiratory Tract Clearance. This portion of the model identifies the principal clearance pathways within the respiratory tract. The model was developed to predict the retention of various radioactive materials. Figure 3-4 presents the compartmental model and is linked to the deposition model (see Figure 3-2) and to reference values presented in Table 3-5. This table provides clearance rates, expressed as a fraction per day and also as half-time (Part A), and deposition fractions (Part B) for each compartment for insoluble... 

If particles reach and become deposited in the alveoli, they tend to stay imbedded in the fluid on the alveolar surface or move into the lymph nodes. The one mechanism by which particles are physically resuspended and removed from the AI region is coughing. For modeling purposes, the AI region is divided into three subcompartments to represent different clearance rates, all of which are slow. 

A clearance rate is defined as the volume of blood or plasma completely cleared of drug per unit time. It is a useful way to describe drug elimination because it is related to blood or plasma perfusion of various organs... 

Example. In the example plotted in Fig. 6, the amount of drug excreted over the 0- to 0.5-hour interval was 37.5 mg. If the plasma concentration at 0.25 hour (the middle of the interval) was lOpg/mL, what was the renal clearance rate From Eq. (18),... 

Drugs can be cleared from the body by metabolism as well as renal excretion, and when this occurs it is not possible to measure directly the amount cleared by metabolism. However, the total clearance rate (TCR), or total body clearance, of the drug can be calculated from its pharmacokinetic parameters using the following equation ... 

When a drug is eliminated by both metabolism and urinary excretion, it is possible to calculate the metabolic clearance rate (MCR) by the difference between TCR and RCR ... 

Example. Kanamycin is a member of the aminoglycoside class of antibiotics, all of which are eliminated exclusively by glomerular filtration. Creatinine is a natural body substance that is cleared almost exclusively by glomerular filtration, and creatinine clearance rate is frequently used as a diagnostic tool to determine glomerular filtration rate. The relationship... 

Fig. 8 Plot of kanamycin clearance rate versus creatinine clearance rate.

Although determination of creatinine clearance rate is a standard clinical procedure, it is difficult to carry out mainly because accurate collection of total urine output over a 24-hour period is required. It can never be certain that this requirement has been met. Since creatinine is produced continuously in muscle and is cleared by the kidney, renal failure is characterized by elevated serum creatinine levels. The degree of elevation is directly related to the degree of renal failure—if it is assumed that the production of creatinine in the muscle mass is constant and that renal function is stable. When these assumptions are valid, there is a direct relationship between serum creatinine level and kanamycin half-life, as shown in Fig. 9. The equation of the line in Fig. 9 is... 

Negatively charged particles are more rapidly cleared from the blood than are neutral and positive ones [75], The clearance rate of particles by the reticuloendothelial system is inversely related to the load of the particles that is, the rate of clearance of a larger dose of microparticulate is slower than for a smaller dose [76],... 

---