Most water-soluble drugs are eliminated from the body through hepatic metabolism. renal filtration, or a combination of the two. It makes sense that the body would aim to make a drug 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 then enter the urine. 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.
An alteration in renal function will have a major effect on the clearance of the drug or its active metabolite(s). Decreased renal function results in elevated serum drug concentrations.