Drugs, drugs, and more drugs… Molecule Monday Drugs, drugs, and more drugs…

Cytochrome P450 Also known as CYPs or P450 Found in all domains of life: animals, plants, fungi, bacteria, viruses, and archaea. But have not been found in E.coli. In AP Bio, we saw them in the electron-transport system (ETS). Catalyze both electron transfer as well as addition of oxygen into organic molecules.

Structure of CYP

CYPs in Humans Responsible for significant majority (75%) of drug metabolism in humans. Large family of enzymes! Humans have 57 different genes for CYP enzymes, but only 6 of them are responsible for approx. 90% of the metabolic activity. Very important to pharmacists, pharmacologists, pharmacokinetics, medicine, biochemists, etc.

P450 Drug Metabolism

Drug Metabolism Most drugs are absorbed in the small intestine, and degraded in the liver. If two drugs are both metabolized by the same P450 enzyme, they will compete and their metabolism will be different then if taken individually. Some drugs induce (activate) P450 synthesis, while others inhibit activity.

Example of Drug Interactions

It Ain’t Just Drugs… Grapefruit juice (and some other fruit juices) inhibit CYP 3A4, which metabolizes estrogen and statins. St. John’s Wort (herbal supplement) activates this same enzyme.

Drug Interactions Clinical trials of new drugs are relatively short, involve only 1 drug, and use a relatively small number of participants. 40 percent of Americans aged 65 or older take more than 5 prescription drugs…so interactions are HIGHLY likely! Estimated 100,000 annual U.S. hospitalizations due to adverse drug interactions.

Hope for the Future Stanford scientist developed a computer program to correlate information from online reports. For example: Prilosec/Prevacid correlates to a 16% increase in risk for heart attack. FDA has created a computer model to try to predict how the metabolism of one drug by P450 will effect the metabolism of a different drug.

Future, cont… Genetic differences cause humans to metabolize drugs differently (personalized medicine). In a recent survey, 17% of pharmacists are now using results from genetic testing (doesn’t need a Rx) to help check for possible drug interactions. Burden of drug interactions is shifting to pharmacists.