finasteride, Propecia
Comparative study of human steroid 5alpha-reductase isoforms in prostate and female breast skin tissues: sensitivity to inhibition by finasteride and epristeride.

Ranjan M, Diffley P, Stephen G, Price D, Walton TJ, Newton RP.

Biochemistry Group, School of Biological Sciences, Wallace Building, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, United Kingdom.

Steroid 5alpha-reductase (5-AR) catalyses the reduction of testosterone (T) to dihydrotestosterone (DHT). The 5alpha-reductase found in human benign prostatic hyperplasia (BPH) has been compared with that found in human breast skin tissue in respect of sensitivity to inhibition by Finasteride and Epristeride. Kinetic studies showed the presence of two isoforms of 5alpha-reductase in benign prostatic hyperplasia indicated by low and high Km isoforms for testosterone, while female breast skin tissue contained only one isoform. The isoforms differ in their affinity for the inhibitors Finasteride and Epristeride, both compounds being more effective for the low Km 5alpha-reductase isoform than the high Km 5alpha-reductase of prostatic tissue, with Finasteride displaying competitive inhibition and Epristeride uncompetitive. Finasteride and Epristeride are also inhibitors of skin 5alpha-reductase, which possesses a comparable Ki for Finasteride to that of the low Km prostatic enzyme, but Epristeride was a less potent inhibitor of the skin enzyme relative to the prostate isoform. These results suggest that the inhibitors have therapeutic potential, other than for treatment of benign prostatic hyperplasia, for treating skin disorders influenced by the action of dihydrotestosterone and warrant further investigation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12031682&dopt=Abstract finasteride Propecia



finasteride, Propecia
Finasteride, a steroid 5 alpha-reductase inhibitor, does not affect the oxidative metabolism of antipyrine.

Winchell GA, Gregoire S, Taylor AM, Hegland J, Hunninghake DB.

Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.

A single-blind study was conducted to investigate the effect of multiple doses of finasteride, a 5 alpha-reductase inhibitor for the treatment of benign prostatic hyperplasia, on the single-dose pharmacokinetics of antipyrine. Twelve patients with benign prostatic hyperplasia received a total of four single oral doses of 18 mg/kg antipyrine before, during, and after treatment with 10 mg/day of finasteride for 28 days. Finasteride had no effect on antipyrine concentration profiles. There were also no changes in urinary excretion of three principal antipyrine metabolites. A slight increase in renal clearance of antipyrine was observed; however, this is not considered relevant because excretion of unchanged antipyrine represents a minor fraction of total elimination and is not directly related to oxidative metabolism. These results imply that significant interactions between finasteride and drugs metabolized by these cytochrome P-450 enzymes are unlikely.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7693768&dopt=Abstract finasteride Propecia



finasteride, Propecia
A rapid method for obtaining finasteride, a 5alpha-reductase inhibitor, from commercial tablets.

Trapani G, Dazzi L, Pisu MG, Reho A, Seu E, Biggio G.

Pharmaco-Chemistry Department, University of Bari, Via Orabona 4, 70125, Bari, Italy. trapani farmchim.uniba.it

To study the effects of allopregnanolone (AP) depletion on stress-induced dopamine changes in cortical dopamine, the 5alpha-reductase inhibitor finasteride on a gram-scale is required. Two procedures for the extraction of finasteride from tablets are outlined (method A and B). In method A, a suspension of powdered tablets was preliminary extracted with chloroform and the extracts dried and evaporated. The resulting residue was then purified on column chromatography. Method B involves a direct chromatographic separation of the powdered tablets. In terms of isolated yields, the second procedure works well, is cheaper, and less time-consuming. The efficiency of the method was tested by measuring progesterone, AP and THDOC content in plasma and cerebral cortex of rats. The protocol enables the prompt availability of sufficient amount of finasteride in experimental grade, useful in examining the role of endogenous cerebrocortical AP in brain homeostasis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12034332&dopt=Abstract finasteride Propecia



finasteride, Propecia
Metabolism of finasteride in rat hepatic microsomes: age and sex differences and effects of P450 inducers.

Ishii Y, Mukoyama H, Hata S.

Drug Metabolism, Development Research Laboratories, Banyu Pharmaceutical Co., Ltd, Saitama, Japan.

1. The age- and sex-related metabolism of finasteride and the effects of P450 inducers and inhibitors were investigated using rat hepatic microsomes. 2. No marked age difference (3-13 weeks) in the rates of finasteride disappearance and the formation of 1 (omega-hydroxyfinasteride) and 4 (6 alpha-OH finasteride) was observed in the male rat. Whereas the rate of 1 formation remained about the same in male rat aged 1 year as compared with rat aged 7 weeks, a 21 and 45% decrease in the rate of finasteride disappearance and 4 formation, respectively, were observed. 3. The rates of finasteride disappearance and metabolite formation 1 and 4 in the female rat decreased with an increase in age (3-7 weeks). Metabolite 4 was hardly formed by the hepatic microsomes from the female rat at 7 weeks of age. 4. Hepatic microsomes from the male rat treated with phenobarbital (PB) and dexamethasone (Dex) increased the rate of the finasteride disappearance (PB, 5.5-fold; Dex, 11.6-fold), whereas no increase in this activity was observed after administration of beta-naphthoflavone (BNF). Similarly, pretreatment of the female rat with PB and Dex resulted in increases of 26.6 and 8.4-fold in the rate of finasteride disappearance, respectively, whereas no inductive effect on this activity was observed in the BNF-treated female rat. 5. These observations suggest that finasteride is metabolized by P4502B, P4502C, and P4503A subfamilies in the male rat and by P4502B and P4502C subfamilies in the female rat.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7810168&dopt=Abstract finasteride Propecia



finasteride, Propecia
Picogram determination of finasteride in human plasma and semen by high-performance liquid chromatography with atmospheric-pressure chemical-ionization tandem mass spectrometry.

Constanzer ML, Chavez CM, Matuszewski BK.

Merck Research Laboratories, West Point, PA 19486.

A method based on high-performance liquid chromatography (HPLC) with atmospheric-pressure positive-ion chemical ionization (APCI)-tandem mass spectrometric (MS-MS) detection for the determination of finasteride (MK-906, I) in human plasma and semen has been developed. The drug and internal standard (II) were extracted from biological matrices using a single solid-phase cyano cartridge. The eluent from the cartridge was injected directly onto the a 33 x 4.6 mm I.D. C18, 3-microns column coupled with a base deactivated C18 20 x 4.6 mm I.D., 5-microns guard column. The column eluate was passed into the corona discharge APCI source by means of a heated nebulizer interface. The analyte and its internal standard were detected using multiple reaction monitoring (MRM) mode for enhanced selectivity and sensitivity. The chromatographic run time was 3 min, and the method had sufficient sensitivity, precision, accuracy and selectivity for the analysis of clinical samples containing finasteride at concentration of 0.2 ng/ml. The assay methodology confirms the versatility of APCI-MS-MS detection, combined with HPLC, for the quantitation of selected drugs in the sub-ng/ml range in biological fluids.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7820256&dopt=Abstract finasteride Propecia



finasteride, Propecia
Biotransformation of finasteride (MK-0906) by Selenastrum capricornutum (green algae).

Venkataramani ES, Carlin JR, Dolling U, Christofalo P, Magliette RJ, Arison BH, Stearns RA.

Merck Research Laboratories, Rahway, New Jersey 07065.

Finasteride (MK-0906), a drug used for the treatment of benign prostatic hyperplasia, is a highly specific inhibitor of steroid 5 alpha-reductase, an enzyme that converts testosterone (T) to dihydrotestosterone (DHT) in animals and humans. In a study to evaluate the effect of finasteride on the growth of green alga, Selenastrum capricornutum, the parent drug was not detected by HPLC in the posttreatment (14 day) samples, suggesting complete biotransformation. Thermospray LC/MS, followed by NMR analysis, indicated that the major algal metabolite was 11 alpha-hydroxy-finasteride. This metabolite has negligible in vitro bioactivity against human prostatic 5 alpha-reductase; its potency is only 2% that of finasteride. The primary metabolite of finasteride produced by the green alga involved a biotransformation not previously observed in mammalian and human studies. The green alga effectively deactivates the drug, thereby mitigating any potential environmental impact.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7832532&dopt=Abstract finasteride Propecia