前列腺体积增大的BPH患者.pptVIP

Tea Break 15 Minutes * * Prostate volume was examined by digital rectal examinations at the screening stage. Figure above number detected by MRI * For the data of Year 2-4, included drop out patients Designing a new drug - Finasteride Many inhibitors of 5 alpha-reductase were developed, from 1975 to 1989 Finasteride is a selective 5α-reductase inhibitor H -reductase O OH Testosterone O OH Dihydrotestosterone H N H O CONHC(CH 3 ) 3 Finasteride NADPH 5 ? Stoner E, Guess H. Treatment of benign prostatic hyperplasia with 5?-reductase inhibitors. The Endocrinologist. 1995;5:1-7. Two isoenzymes of 5- alpha-reductase in males were found to be encoded by two different genes. According to the finding order, these two isoenzymes were named type I and type II 5 alpha-reductase respectively. It was confirmed later by genetic researches that steroid 5- alpha-reductase deficiency was caused by the genetic mutation of type II 5 alpha-reductase. 1992 Jenkins EP, et al. Genetic and pharmacological evidence for more than one human steroid 5 alpha-reductase. J Clin Invest. 1992;89:293-300. Russell DW, Wilson JD. Steroid 5a-reductase: two genes/two enzymes. Annu Rev Biochem. 1994;63:25-61. Two isoenzymes of 5-alpha-reductase were found Different isoenzymes of 5- alpha-reductase have different target organs Type II isoenzyme of 5α-reductase * Type I isoenzyme of 5α-reductase *inherited deficiency Scalp Face Skin (chest/back) Liver Adrenal Kidney Subcutaneous glands Brain Scalp and hair follicle Beard Skin of the chest seminal vesicle Prostate Epididymis Foreskin/scrotum Liver Treated with finasteride for 7 days, the DHT level in the prostatic tissues decreased significantly Placebo 5 mg 10 mg 50 mg 100 mg DHT level in prostatic tissue (ng/g) 1 2 0 3 4 5 Finasteride, a 5-alpha-reductase inhibitor, reduces DHT in prostate, which might block prostate growth Respond sequence to the treatment with finasteride DHT Inhibition Accelerating urine flow Progress