Subject sildenafil

Sildenafil GFJ (1 subject) AUC Cmax T, Tmax C/2 Blood pressure (193)... 

Potentiation by sildenafil of the hypotensive effects of glyceryl trinitrate and amlodipine has been investigated. The fall in systolic blood pressure with glyceryl trinitrate was amplified four-fold by sildenafil in healthy subjects. 

A, Naso C, et al. 2002. Effects of sildenafil citrate (viagra) on cardiac repolarization and on autonomic control in subjects with chronic heart failure. Am. Heart J. 143 703-10... 

D. J. Nichols, G. J. Muirhead, and J. A. Harness, Pharmacokinetics of sildenafil after single oral doses in healthy male subjects absolute bioavailability, food effects and dose proportionality. Br J Clin Pharmacol 53(Suppl 1) 5S-12S (2002). 

Sildenafil inhibits phosphodiesterase isoenzyme type 5 in platelets, which theoretically could inhibit platelet aggregation. Although sildenafil has not caused bleeding in healthy subjects, it should be used cautiously in patients taking aspirin or other antiplatelet agents and in patients with bleeding tendencies. 

Sildenafil, tadalafll and vardenafil do not usually alter the effects of alcohol on blood pressure, although postural hypotension has been seen in some subjects given tadalafll and alcohol, and headache and flushing has been reported in one patient taking sildena-... 

Sildenafil does not appear to affect the pharmacokinetics of tacrolimus. The levels of sildenafil were higher in patients taking tacrolimus than in healthy subjects, but it is not clear whether this was due to tacrolimus alone. A marked blood pressure drop occurred when both drugs were given in one study. 

In a single dose study in 12 healthy subjects the bioavailability of sildenafil was not affected by single 30-rnL doses of an aluminium/magnesium hydroxide antacid. ... 

When sildenafil 100 mg was given to hypertensive patients taking am-lodipine the mean additional fall in blood pressure (8/7 mmHg) was of the same magnitude as that seen when sildenafil was given alone to healthy subjects. ... 

In an open label, randomised study in 12 healthy subjects, ketoconazole 200 mg daily increased the AUC of a single 10-mg dose of tadalafil by twofold, and ketoconazole 400 mg daily increased the AUC fourfold. The manufacturers predict that itraconazole will interact similarly. This prediction has been borne out by a case report of a 56-year-old man who was taking itraconazole 400 mg daily for 7 days each month. Within a few hours of his first 10-mg dose of tadalafil he developed priapism, which lasted for more than 4 hours. The same reaction occurred when he took tadalafil during the following month. He had seemingly previously taken sildenafil with itraconazole without adverse effect. ... 

Grapefruit juice 250 mL was given to 24 healthy subjects both one hour before and with a 50-mg dose of sildenafil. The AUC of sildenafil was... 

In a study in 24 healthy subjects, erythromycin 500 mg twice daily for 5 days was found to increase the AUC of single 100-mg doses of sildenafil almost threefold. In the same study, azithromycin 500 mg once daily for 3 days had no effect on the pharmacokinetics of sildenafil. In another study, in 12 healthy subjects, clarithromycin 500 mg increased the AUC of sildenafil 50 mg 2.3-fold, and the maximum level 2.4-fold. ... 

In a limited and preliminary study it was reported that no blood pressure alteration was seen when a small dose of glyceryl trinitrate (amount not specified) was given as a dermal patch while subjects were taking 50 mg of sildenafil. In addition, the beneficial effects of the glyceryl trinitrate on the radial artery pressure waveform were approximately doubled, and persisted for up to 8 hours. ... 

In a randomised, plaeeho-eontrolled, double-blind, crossover study, 28 healthy subjects were given sildenafil 100 mg before and after taking ritonavir for 7 days (300,400 and 500 mg twice daily on days 1, 2 and 3 to 7, respectively). It was found that the sildenafil AUC was increased 11-fold and the maximum serum levels 3.9-fold by ritonavir, but the inci-denee and severity of the sildenafil adverse effects and the steady-state levels of ritonavir remained unchanged. However, the clinical significance of this interaction is highlighted by a case report of a 47-year-old man, with no cardiovascular risk factors apart from smoking, who had a fatal heart attack when he took sildenafil 25 mg while he was also taking ritonavir and saquinavir. One hour after the ninth dose, he had an onset of severe ehest pain, and died soon after. ... 

The manufacturer notes that population pharmacokinetie analysis of elin-ical study data indieate that inhibitors of cytochrome P450 isoenzyme CYP2D6 such as SSRIs and tricyclic antidepressants do not have any effect on the pharmacokinetics of sildenafil. However, in a double-blind, placebo-controlled study in healthy subjects, pre-treatment with fluvox-amine 50 mg daily for 3 days then 100 mg daily for 6 days increased the AUC of sildenafil 50 mg by 40%. This resulted in an inerease in the vascular effects of sildenafil. ... 

In 10 patients with pulmonary hypertension, bosentan 62.5 mg twice daily for one month decreased the AUC of a single 100-mg dose of sildenafil by 53% and increased its clearance 2.3-fold. After a second month of bosentan at an increased dose of 125 mg twice daily, the AUC of a single 100-mg dose of sildenafil was reduced by 69%, and the clearance increased 3.4-fold. The AUC of the primary metabolite, desmethyl-sildenafil, was also decreased in a dose-dependent manner by bosentan. In a further study in healthy subjects, the concurrent use of bosentan 125 mg twice daily and sildenafil 80 mg three times daily for 6 days decreased the AUC of sildenafil by 63%. ... 

Sensory systems Adverse effects of PDE-5 inhibitors on the eyes have repeatedly been reported, but it is unclear whether these events are coincidental or related to drug-related effects on the ocular circulation or on other structures in the eye [27 ]. In a multicenter study 244 subjects were randomized to tadalafil 5 mg/day, sildenafil 50 mg/day, or placebo for 6 months [28. There was one case of retinal artery occlusion in a patient taking placebo and there were no abnormalities in electroretinogra-phy or visual function and no treatment-related findings suggestive of drug toxicity. 

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