Of the two biotransformation systems through which hepatic metabolism occurs, it is the cytochrome P450 system (Phase I) most affected by increasing years. For most drugs, this leads to increased serum levels of the unmetabolized entity, leading to a greater potential for toxicity. Disease states that reduce blood flow to the liver, like congestive heart failure and cirrhosis, further inhibit this process. For drugs whose pharmacological activity requires biotransformation from a pro-drug form, inhibition can lead to decreased efficacy.