Some drugs and many drug metabolites are excreted by the kidneys. Renal clearance is the rate of elimi-nation of a drug from the body by kidney excretion. This concept is analogous to hepatic clearance, and similarly, renal clearance can be expressed as the renal blood flow times the renal extraction ratio.
Small unbound drugs freely pass from plasma into the glomerular filtrate. The nonionized(uncharged) fraction of drug is reabsorbed in the renal tubules, whereas the ionized (charged) portion is excreted in urine. The fraction of drug ionized depends on the pH; thus renal elimination of drugs that exist in ionized and nonionized forms depends in part on urinary pH. The kidney actively secretes some drugs into the renal tubules.
Many drugs and drug metabolites pass from the liver into the intestine via the biliary system. Some drugs excreted into the bile are then reabsorbed in the intestine, a process called enterohepatic recircu-lation. Occasionally metabolites excreted in bile aresubsequently converted back to the parent drug. For example, lorazepam is converted by the liver to loraz-epam glucuronide. In the intestine, β-glucuronidase breaks the ester linkage, converting lorazepam gluc-uronide back to lorazepam.