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Drug metabolism mainly takes place in the liver, while excretion mainly takes place in the kidneys. Following drug administration, drugs must pass through tightly packed cells, crossing cell membranes to reach their sites of action. Usually drugs are lipophilic or fat soluble compounds, and cell membranes are composed of phospholipids, so drugs are able to cross them. However, for excretion by the kidneys, it's necessary to convert drugs to water soluble or hydrophilic compounds. Drugs are usually administered orally or parenterally. Parenteral drugs bypass the digestive tract. Parental routes include injection, transdermal patches, lotions, inhalants, and suppositories. If injected, the drugs reach general circulation quickly and have an immediate effect. If taken orally, drugs must pass through the cells of the gastrointestinal tract. Drugs cross through cells of the GI tract and travel to the liver via the hepatic portal vein. The liver has a chance to metabolize some of the drug before it goes into general circulation, this is called the first pass effect. In the liver, drugs enter hepatic cells where a series of enzymes in smooth endoplasmic reticulum metabolize them. Drugs move through the phospholipid membrane of endoplasmic reticulum. Hepatic microsomal enzymes such as p450 convert drugs from lipophilic to hydrophilic compounds. Repeated use of certain drugs increases the amount of metabolic enzymes and increases drug metabolism. This is called enzyme induction. Conversely, certain drugs compete to bind to metabolic enzymes thereby decreasing drug metabolism. This is called enzyme inhibition. Once metabolized, these hydrophilic metabolites leave the cell ready for excretion by the kidney. A drug's duration and intensity of effect are largely determined by metabolic rate. Increased metabolic rate will decrease drug duration and intensity by facilitating excretion. 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