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| 지원과제 | BMRC |
| 저자명 | Shon JH, Ku HY, Bae SY, Oh MK, Yeo CW, Bae SK, Shin JG. |
| 학회정보 | Pharmacogenet Genomics. 21(12):820-8 / 2011.12 |
| 제 목 | The disposition of three phosphodiesterase type 5 inhibitors, vardenafil, sildenafil, and udenafil, is differently influenced by the CYP3A5 genotype. |
| LINK | www.ncbi.nlm.nih.gov/pubmed/21934637 |
| 게시일 | 2014-02-12 14:08:27 |
| 년도 | 2011-International |
| 내용 | Abstract
OBJECTIVES: This study was conducted to compare the effect of CYP3A5*3 genotype on the disposition of three phosphodiesterase type 5 inhibitors (PDE5Is), vardenafil, sildenafil, and udenafil, because our previous in-vitro microsomal incubation study showed that the relative contribution of CYP3A5 enzyme to their metabolism was different among these PDE5Is. METHODS: An open-label three-way crossover study was performed with a single oral dose of PDE5Is (20 mg vardenafil, 100 mg sildenafil, or 200 mg udenafil) in 21 healthy men carrying CYP3A5*1/*1, *1/*3, or *3/*3. After each dose, plasma concentrations of the parents and their major metabolites were measured up to 24 or 48 h. RESULTS: The AUC(∞) and C(max) of vardenafil were 2.9-fold and 3.1-fold higher in CYP3A5*3/*3 carriers than in individuals with CYP3A5*1/*1 (P=0.003 and 0.002, respectively). The AUC(∞) and C(max) of sildenafil were 1.5-fold and 1.7-fold higher in CYP3A5*3/*3 carriers compared with individuals with CYP3A5*1/*1, but the statistical difference of both parameters among genotype groups was not observed. The disposition of udenafil differed little among groups in relation to the CYP3A5*3 allelic variant. CONCLUSION: These results suggest that the disposition of these PDE5Is are differently influenced by the CYP3A5*3 genotype of individual participants. The CYP3A5*3 genotype affects the oral disposition of vardenafil significantly. The pharmacokinetic diversity of PDE5Is in relation to CYP3A5 genotype may lead to the clinical response variation and remains to be evaluated. |
