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Drug-metabolizing enzymes and transporters: expression in the human prostate and roles in prostate drug disposition.

Local biotransformation enzymes and transporter proteins in tissues may exert a profound effect on drug pharmacokinetics in those tissues. Thus, the use of drugs for the treatment of benign prostatic hyperplasia (BPH) and cancer of the prostrate may be influenced by high level expression of cytochrome P450 (CYP) phase I and phase II conjugation enzymes and drug transporters. Phase I drugmetabolizing enzymes detected in the human prostate include CYP, CYP1A1, CYP1A2, CYP1B1, CYP2C19, CYP2D6, CYP3A5, and CYP4B1 in both normal and tumorous tissue; CYP1A1, CYP1A2, and CYP1B1 in BPH tissues; and CYP1A1 and CYP1A2 in prostate cancer cell lines and normal prostate epithelial cells. Epoxide hydrolase was also found in prostate tumor and nonneoplastic tissue. Phase II metabolizing enzymes detected in the prostate were glutathione S-transferases (GSTs) GST-a, GST-m, and GST-p, and N-acetyltransferase (NAT) isoforms, NAT1 and NAT2. Prostate tissue contains the multidrug resistance protein (MRP) transporters MRP1, MRP2, MRP3, and MRP4, and the multidrug resistance (MDR)-1 protein (P-glycoprotein; P-gp). Metabolism of drugs used in BPH (eg, finasteride and tamsulosin) and anticancer agents have been examined in the liver or liver preparations but not in the prostate or prostate tissue/cell lines. Thus, the published data to date shows that the prostate contains the major phase I and II drug-metabolizing enzymes as well as drug transporters. Future studies should examine the ability of the prostate to metabolize drugs used in either BPH or prostate cancer and to gauge the ability of the identified drug transporters to facilitate