2006
DOI: 10.1016/j.ijpharm.2006.04.005
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Pharmacokinetics of sildenafil after intravenous and oral administration in rats: Hepatic and intestinal first-pass effects

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Cited by 56 publications
(44 citation statements)
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“…Obviously, a dose response study should be explored in this experimental nerve resection model using retrolingual daily doses, although the pharmacokinetics of sildenafil clearance may require a higher dose. 37,39 Cavernosal nerve damage and sildenafil I Kovanecz et al Based on these current findings in the UCNR and BCNR models with sildenafil and those previously with vardenafil in the BCNR model, together with that observed in the aged rat treated with sildenafil, we believe that the PDE5 inhibitors possess antifibrotic activity which in the penile tissue may lead to the prevention or delay in the onset or progression of CVOD regardless of its etiology. 33,12 Although cGMP was not estimated in the penile tissue in this study because the rats were killed after a 24 h washout, we assume that the high cGMP levels generated by PDE5 inhibitors are what counteracts fibrosis and protects the corporal smooth muscle.…”
Section: Discussionsupporting
confidence: 65%
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“…Obviously, a dose response study should be explored in this experimental nerve resection model using retrolingual daily doses, although the pharmacokinetics of sildenafil clearance may require a higher dose. 37,39 Cavernosal nerve damage and sildenafil I Kovanecz et al Based on these current findings in the UCNR and BCNR models with sildenafil and those previously with vardenafil in the BCNR model, together with that observed in the aged rat treated with sildenafil, we believe that the PDE5 inhibitors possess antifibrotic activity which in the penile tissue may lead to the prevention or delay in the onset or progression of CVOD regardless of its etiology. 33,12 Although cGMP was not estimated in the penile tissue in this study because the rats were killed after a 24 h washout, we assume that the high cGMP levels generated by PDE5 inhibitors are what counteracts fibrosis and protects the corporal smooth muscle.…”
Section: Discussionsupporting
confidence: 65%
“…Rats were subjected to cavernosometry after a 24 h washout period that reduces sildenafil concentrations to baseline. 12,39 Rats undergoing UCNR and BCNR for 45 days had a significant increase in the drop rate as compared to sham-operated animals, which was higher after BCNR than UCNR (Figure 1 bottom), and this was accompanied by a significant reduction of the response to papaverine (top), but only in the BCNR rats. This confirmed our previous observation that CVOD is induced by BCNR, and showed that UCNR induced a moderate CVOD.…”
Section: Resultsmentioning
confidence: 98%
“…The rapid and extensive CMDCK metabolism mediated by CYP3A4 and CYP3A5 might lead to low bioavailability in the human body [19,20] . In general, a higher conversion rate of a drug candidate in vitro is unfavorable because the conversion rate is predictive of higher hepatic clearance in vivo, resulting in a significant first pass effect for oral administration [21] . In fact, a number of clinically available anti-HIV agents exhibit significant firstpass hepatic metabolism.…”
Section: Discussionmentioning
confidence: 99%
“…The study gro up (SG, n= 50) was ad mi nis te red sil de na fil (Vi ag ra ® Pfi zer, İs tan bul, Tur key; 10 mg/kg on ce a day for 10 days) vi a an oro gas tric tu be, un til 12 h be fo re sur gery. Sil de nafil (dis sol ved in dis til led wa ter with a mi ni mum amo unt of HCl and ad jus ted to a fi nal pH of ap proxi ma tely 4 with Na OH at do ses of 10 mg/kg body we ight/day) was gi ven to rats orally using the method des cri bed by Shin et al 15 Each rat was anest he ti zed with an in tra muscu lar in jec ti on of 60 mg/kg of ke ta mi ne hydrochlo ri de (Ke ta lar, Ec za cı ba sı, War ner-Lam bert La bo ra to ri es, Le vent, Is tan bul, Tur key) and 10 mg/kg of xyla zi ne hydroch lo ri de (Rom pun, Ba yer La bo ra to ri es, Sis li, Is tan bul, Tur key). All pro ce dures we re per for med un der cle an but nons te ri le condi ti ons.…”
Section: Ma Te Ri Al and Met Hodsmentioning
confidence: 99%