Most water soluble drugs are eliminated from the body through hepatic metabolism followed by renal filtration. It makes sense that the body would ultimately want a drug to be water soluble. When a small molecular-weight compound is water soluble, it can be excreted from the blood by simple filtration through the kidneys and it will quickly be found in the urine. But since fatty, nonpolar molecules do not dissolve in water they tend to accumulate in tissues or bind strongly to proteins. Until the body can render these molecules water soluble, they are much less likely to be excreted.
Since the kidneys ultimately mediate the removal of most drugs from the body, it is not surprising that any alteration in renal function can have a major effect on the clearance of a drug or its active metabolite(s). Decreased renal function results in elevated serum drug concentrations.
