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We know that many drugs interact with each other and do so by
dealing with some of the enzymes in this pathway, and Kliewer and his colleagues reasoned
that one of the enzymes that St. John’s Wort may be dealing with is known as cytochrome
P4-53A, or CYP3A. This is an enzyme that we know can oxidize a particular drug, promoting
its excretion. Birth control pills and cyclosporin, the drug important for preserving transplants, as well as indinavir are targets of CYP3A, and CYP3A activity will speed the metabolism of those drugs. Now, the question is what regulates the expression of CYP3A? It comes from a gene that’s regulated by an upstream promoter, and various drugs can induce binding of nuclear receptors to that promoter, increasing expression of CYP3A, increasing the accelerated metabolism of these drugs. The kinds of drugs that we know can up regulate the expression of CYP3A include rifampicin, the tuberculosis drug; steroids, diabetes drug, the anti-epilepsy drug Phenytoin, the cancer drug, Taxol, and possibly -- and this was the purpose of this work –- St. John’s wort as well. |