Browse > Article
http://dx.doi.org/10.4333/KPS.2006.36.4.223

Preparation and Evaluation of PGE1-ethyl Ester Intraurethral Solutions for Erectile Dysfunction  

Choi, Han-Gon (College of Pharmacy, Yeungnam University)
Yoo, Bon-Kyu (College of Pharmacy, Yeungnam University)
Rhee, Jong-Dal (College of Pharmacy, Yeungnam University)
Kim, Jung-Ae (College of Pharmacy, Yeungnam University)
Kwon, Tae-Hyub (College of Pharmacy, Yeungnam University)
Woo, Jong-Soo (College of Pharmacy, Yeungnam University)
Yong, Chul-Soon (College of Pharmacy, Yeungnam University)
Publication Information
Journal of Pharmaceutical Investigation / v.36, no.4, 2006 , pp. 223-229 More about this Journal
Abstract
[ $PGE_1$ ]-ethyl ester intraurethral solutions were prepared in ethanol/propylene glycol mixture with penetration enhancer and viscosity-enhancing agent. The stability of $PGE_1$-ethyl ester in intraurethral solution was investigated at various temperature. Simultaneous determination of $PGE_1$-ethyl ester and $PGE_1$ was performed using a validated HPLC technique. In pentobarbital anesthetized cats, increase in intracavernous pressure(ICP), increase in penile length and duration of erectile response were determined after intraurethral application of $PGE_1$-ethyl ester solutions. $PGE_1$-ethyl ester solutions, when instilled into the eyes of rabbits, produces no noticeable irritation, or slight transient conjunctival irritation. From these results, ocular irritation of this solutions was judged as practically non-irritating. The stability study indicates that the therapeutically effective content in solution is well maintained for 46 weeks or longer when they are stored at $4^{\circ}C$. After intraurethral application of $PGE_1$-ethyl ester, ICP was increased and penile erection was induced. $PGE_1$-ethyl ester intraurethral solutions for erectile dysfunction could be developed and evaluated by employing feline erection model.
Keywords
$PGE_1$-ethyl ester; Erectile dysfunction; Intraurethal solution; Feline model;
Citations & Related Records
연도 인용수 순위
  • Reference
1 NIH concensus conference. Development panel on impotence: impotence, JAMA, 270, 83-90 (1993)   DOI
2 R. G. Stehle and T. O. Oesterling, Stability of prostaglandin $E_1$ and dinoprostone(prostaglandin $E_2$) under strongly acidic and basic condition, J. Pharm. Sci., 66, 1590-1595 (1977)   DOI
3 D. C. Monkhouse, L. Van Campen and A. J. Aguiar, Kinetics of dehydration and isomerization of prostaglandins $E_1$ and $E_2$, J. Pharm. Sci., 62, 576-580 (1973)   DOI
4 G. Williams, C.-C. Abbou, E. T. Amar, P. Desvaux, T. A. Flam, G. A. B. Lycklama a Nijeholt, S. F. Lynch, R. J. Morgan, S. C. Muller, H. Porst, J. P. Pryor, P. Ryan, U. K. F. Witzsch, M. M. Hall, V. A. Place, A. P. Spivack and N. Gesundheit, Efficacy and safety of transurethral alprostadil therapy in men with erectile dysfunction. Brit. J. Urol., 81, 889-894 (1998)   DOI
5 N. Aoyagi, N. Kaniwa and M. Uchiyama, Inter-laboratory reproducibility of release tests for suppositories, Drug. Develop. Ind. Pharm., 21, 176-183 (1995)
6 A. Babar, H. M. Fares and F. M. Plakogiannis, In vitro release of testosterone from suppository bases and in vivo absorption studies in human males, J. Pharm. Sci., 83, 389-391 (1993)
7 P. Halter, Trends in urology, Med. Device Diagn. Industry, 12, 52-54 (1990)
8 L. Garcia-Reboll, J. P. Mulhall and I. Goldstein, Drugs for the treatment of impotence, Drugs & Aging, 11, 140-151 (1997)   DOI   ScienceOn
9 H. C. Champion, T. J. Bivalacqua, R. Wang, P. J. Kadowitz, L. K. Keefer, J. E. Saavedra, J. A. Hrabie, P. C. Doherty and W. J. G. Hellstrom, Induction of penile erection by intracavernosal and transurethral administration of novel nitric oxide donors in the cat, J. Urol., 161, 2013-2019 (1999)   DOI   ScienceOn
10 R. E. Nellans, L. R. Ellis and D. Kramer-Levien, Pharma- cological erection: diagnosis and treatment applications in 69 patients, J. Urol., 138, 52-54 (1987)   DOI
11 J. R. White and R. K. Campbell, Drug induced male sexual dysfunction. U.S. Pharmacist Diabetes Supplement. Complications, November, 44-47 (1990)
12 H. Porst, The rationale for prostaglandin $E_1$ in erectile failure: a survey of worldwide experience, J. Urol., 155, 802-815 (1996)   DOI   ScienceOn
13 O. I. Linet and F. G. Orrinc, Efficacy and safety of intraca- vernosal alprostadil in men with erectile dysfunction, N. Engl. J. Med., 334, 873-877 (1996)
14 H. Wendel and F. J. Braun, Transdermal prostaglandin composition, US Patent 5,380,760, 1995
15 M.-T. Sheu, L.-H. Lin, B. W. Spur, P. Y.-K. Wong and H.-S. Chiang, Investigation of the percutaneous penetration of prostaglandin $E_1$ and its ethyl ester, J. Control. Rel., 55, 153-160 (1998)   DOI   ScienceOn
16 J. T. Carstensen, Drug stability, principles and practices, second edition, Marcel Dekker, Inc., New York. 35-48, 1995
17 W. J. G. Hellstrom, R. Wang, P. J. Kadowitz and F. R. Domer, Potassium channel agonists cause penile erection in cats, Int. J. Impot. Res., 53, 1365-1372 (1992)
18 R. Wang, F. R. Domer, S. C. Sika, P. J. Kadowitz and W. J. Hellstrom, Nitric oxide mediates penile erection in cats, J. Urol., 151, 234-237 (1994)   DOI
19 H. C. Champion, R. Wang, W. J. Hellstrom and P. J. Kadowitzs, Noclceptin, a novel endogenous ligand for the ORL1 receptor, has potent erectile activity in the cat, Am. J. Physiol., 273, E214-E219 (1997)   DOI
20 E. D. Kim and K. T. Mcvary, Topical prostaglandin $E_1$ for the treatment of erectile dysfunction, J. Urol., 153, 1828-1830 (1995)   DOI   ScienceOn
21 H. Padma-Nathan, W. J. Hellstrom, F. E. Kaiser, R. F. Labasky, T. F. Lue, W. E. Nolten, P. C. Norwood, C. A. Peterson, R. Shabsigh, P. Y. Tam, V. A. Place and A. Gesundheit, Treatment of men with erectile dysfunction with transurethral alprostadil. Medicated Urethral System for Erection(MUSE) Study Group, N. Engl. J. Med., 336, 1-7 (1997)   DOI   ScienceOn
22 H. C. Champion, R. Wang, J. A. Santiago, W. A. Murphy, D. H. Coy, P. J. Kadowitz and W. J. G. Hellstrom, Comparison of responses to adrenomedullin and calcitonin gene-related peptide in the feline erection model, J. Androl., 18, 513-521 (1997)