The impact of these adverse reactions is that there are estimates from some studies that 6.7% of hospitalized patients in the developed nation like the United States of America have a serious drug reaction with a fatality rate of 0.32%, and there are estimates that put the cost to the nation of the morbidity and mortality related to adverse drug reactions at $136 billion. (1). An essential factor in the toxicity of a drug is the manner in which it is metabolized and excreted from the body. Understanding drug toxicity requires an understanding of the metabolism of drugs in the human body, and the role that it plays in the toxicity of drugs.
Metabolism of drugs occurs after absorption of the drug and hence the route of administration and the absorption of the drug have a role to play in its metabolism. In oral administration of a drug, not all the drug is absorbed. Digoxin is a typical example with only seventy percent of the drug absorbed. This deficient absorption in the gut has been attributed to bacterial metabolism in the intestine and the drug being too hydrophilic or lipophilic. Another factor that has been identified in the poor absorption of a drug in the gut is the role of the reverse transporter associated with P-glycoprotein, which actively pumps the drug out from the gut wall into the gut lumen. Inhibition of this action of the reverse transporter even by nutrients like grapefruit juice leads to more absorption of the drug. (2).
Subsequent to the absorption of the drug, the portal blood system delivers the drug into the liver, before it can enter the systemic circulation. While the gut wall and the portal blood have the capacity for metabolizing the drug, it is essentially the liver that takes over the function of drug metabolism in what is known as the first-pass loss or elimination. (2). Drugs that are administered through other routes like injection or inhalation avoid this first-pass effect of the liver and circulate in the body before reaching the liver.