Excretion overall elimination clearance

Excretion - Renal elimination accounted for about 40% of the overall clearance regardless of the route of administration. The elimination half-life is about 1.4 hours. 

Clearance is a measure of the volume of plasma that is cleared of drug per unit time (see Chapter 3). The total clearance for most drugs is the sum of clearances via excretion by the kidneys and metabolism by the liver. In planning a detoxification strategy, it is important to know the contribution of each organ to total clearance. For example, if a drug is 95% cleared by liver metabolism and only 5% cleared by renal excretion, even a dramatic increase in urinary concentration of the drug will have little effect on overall elimination. 

The renal drug clearance, as the major excretion route, is influenced to different extents by urine flow, urine pH and plasma protein binding. The extent of sensitivity to these parameters depends on the nature of compounds and mechanisms involved in its renal elimination (e.g. glumerular filtration, active secretion, passive re-absorption). Thus, interindividual variation in these parameters together with renal function determines the overall renal clearance, The urine flow is sensitive to individual fluid intake and administration of diuretic drugs. Interindividual differences in urine pH are mainly related to differences in diet and physical activity. 

The next section is a summary of the bioavailability/pharmacokinetic data and the overall conclusions. The summary should include a table with the following pharmacokinetic parameters peak concentration (Cmax), AUC, time to reach peak concentration (Tmax), elimination constant (kel), distribution volume (Vd), plasma and renal clearance, and urinary excretion. Overall conclusions as well as any unresolved problems should be discussed. 

Total clearance Is the sum of all sources of clearance (eg, renal excretion plus hepatic metabolism plus respiratory and skin excretion plus dialysis). If the contribution of dialysis is small compared with the total clearance rate, then the procedure will contribute little to the overall elimination rate (Table 1-40). 

Systemic (Cls) or total body clearance (TBC). This is the sum of all individual organ clearances that contribute to the overall elimination of drugs. However, the organ clearance that can be routinely determined independently in humans is renal clearance because this is the only organ for which we can easily determine an elimination rate. The process of drug removal is called elimination, which may include both excretion and metabolism for a particular drug. 

Salicylate and its metabolites are rapidly and almost completely excreted in the urine by glomerular filtration and by renal tubular secretion. Passive reabsorption of salicylate occurs in the distal tubules. Salicylate elimination is saturable and characterized by Michaelis-Menton kinetics where the elimination half-life is dependent on the dose. Since the pRa of salicylic acid is 3, its renal clearance is greatly influenced by changes in urinary pH. Increasing urinary pH can significantly increase the overall salicylate elimination rate via ion trapping. 

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