Release kinetics of liposome-encapsulated ganciclovir after intravitreal injection in rabbits.

Release kinetics of liposome-encapsulated ganciclovir after intravitreal injection in rabbits. This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped ganciclovir could prolong intraocular therapeutic levels when it is compared to the intravitreal injection of a simple solution of the drug. New Zealand white rabbits were given an intravitreal injection of the drug solution and of liposome-encapsulated ganciclovir. The intravitreal clearance of ganciclovir was determined after a single injection of either the drug solution (200 micrograms/0.1 mL) or the liposomally-entrapped (with 41% load; 82 micrograms drug load and 118 micrograms free) ganciclovir. The ganciclovir vitreal concentrations were measured at various time intervals for a period up to 43 days using an HPLC method. The results of this study clearly demonstrated that prolonged intravitreal drug levels (above the mean inhibitory dose of cytomegalovirus of 1 microgram/mL) after administration of the liposome-entrapped ganciclovir and estimated to continue beyond 30-43 days. The injection of the 200 micrograms/0.1 mL of drug solution showed a mean vitreous concentration which was higher than the ID50 only for 55 h. The disappearance rate constant for the liposome-encapsulated injections was approximately 22 x slower than simple drug solution injections (controls). No evidence of retinal toxicity was found by clinical or light microscopy examination of the treated eyes. Journal ISSN: 0265-2048 Issue: 13-4 (1996 Jul-Aug) Pages: 473-80

Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study.
Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study. OBJECTIVE: This study evaluated the efficacy and safety of vardenafil treatment for erectile dysfunction (ED) in men with diabetes. RESEARCH DESIGN AND METHODS: In this prospective multicenter double-blind placebo-controlled fixed-dose parallel-group phase III trial, 452 patients with diabetes (type 1 or type 2) and ED were randomized to take 10 or 20 mg vardenafil or placebo as needed for 12 weeks. Efficacy responses were assessed by International Index of Erectile Function domain scores, rates of vaginal penetration and successful intercourse, and a global assessment question (GAQ) about erection improvement during the previous 4 weeks. RESULTS: After 12 weeks of treatment, a dose-dependent (P = 0.02) improvement in erections was noted for the GAQ, with 57 and 72% of men taking 10 mg or 20 mg vardenafil, respectively, reporting improved erections, in contrast to 13% after taking placebo (P < 0.0001). For the erectile function domain, dose-dependent (P = 0.03) final scores for the 10- and 20-mg dose were 17.1 and 19.0 compared with 12.6 for placebo (P < 0.0001). Both vardenafil doses significantly enhanced the rates of successful penetration (P < 0.0001) and successful intercourse (P < 0.0001) compared with placebo. Vardenafil treatment was effective in increasing intercourse success rates at all levels of baseline ED severity, at each level of plasma HbA(1c), and for type 1 and 2 diabetes. Treatment-emergent adverse events were primarily mild to moderate headache (

Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction in patients with diabetes mellitus.
Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction in patients with diabetes mellitus. Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has become a first-line therapy for diabetic patients with erectile dysfunction (ED). The efficacy in this subgroup, based on the Global Efficacy Question, is 56% vs 84% in a selected group of non-diabetic men with ED. Two novel PDE5 inhibitors, tadalafil (Lilly ICOS) and vardenafil (Bayer), have recently completed efficacy and safety clinical trials in @apos;general@apos; and diabetic study populations and are now candidates for US FDA approval. A summary analysis of the phase three clinical trials of sildenafil, tadalafil and vardenafil in both study populations is presented to provide a foundation on which the evaluation of the role of the individual PDE5 inhibitors for the treatment of patients with ED and DM can be built. Journal ISSN: 0955-9930 Issue: 14-6 (2002) Pages: 466-71

The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease.
The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease. OBJECTIVES: The effect of vardenafil, a potent and highly selective phosphodiesterase-5 (PDE5) inhibitor, on symptom-limited exercise time, time to first awareness of angina, and time to ischemic threshold (ST-segment depression > or =1 mm from baseline) during exercise tolerance testing (ETT) was examined in patients with stable coronary artery disease (CAD). BACKGROUND: Erectile dysfunction (ED) is common among men with CAD. PDE5 inhibition is increasingly the preferred treatment option for ED. However, the effect of PDE5 inhibition on exercise-induced ischemia in CAD patients has received limited prospective evaluation. METHODS: In this double-blind, crossover, single-dose multicenter study, 41 men with reproducible stable exertional angina due to ischemic CAD received vardenafil 10 mg or placebo, followed by ETT (5 to 10 metabolic equivalents [METS], Bruce protocol) 1 h postdose. Sublingual nitrate use was prohibited for > or =24 h pre- and postexercise study days. End points included symptom-limited treadmill exercise time, time to first awareness of angina, time to ischemic threshold, and safety. RESULTS: Relative to placebo, vardenafil 10 mg did not alter exercise treadmill time (427 +/- 105 s vs. 433 +/- 109 s, p = 0.39), or time to first awareness of angina (292 +/- 110 s vs. 291 +/- 123 s, p = 0.59), but significantly prolonged time to ischemic threshold (334 +/- 108 s vs. 381 +/- 108, p = 0.0004). At peak exercise, vardenafil 10 mg did not alter blood pressure, heart rate, or rate-pressure product relative to placebo. The most common adverse events (facial flushing and headache) were of mild or moderate intensity, and short-lived. CONCLUSIONS: Vardenafil 10 mg did not impair the ability of patients with stable CAD to exercise at levels equivalent or greater than that attained during sexual intercourse (average of 2.5 to 3.3 METS). Journal ISSN: 0735-1097 Issue: 40-11 (2002) Pages: 2006-12

Non-narcotic analgesic dose and risk of incident hypertension in US women.
Non-narcotic analgesic dose and risk of incident hypertension in US women. Acetaminophen, ibuprofen, and aspirin are the most commonly used drugs in the United States. Although the frequency of their use has been associated with hypertension, prospective data examining the dose of these drugs and risk of hypertension are lacking. Furthermore, whether certain indications for analgesic use, particularly headache, mediate the association is unclear. We conducted 2 prospective cohort studies among older women 51 to 77 years of age (n=1903) from the Nurses' Health Study I and younger women 34 to 53 years of age (n=3220) from the Nurses' Health Study II who completed detailed supplemental questionnaires pertaining to their analgesic use and who did not have hypertension at baseline. We analyzed incident hypertension according to categories of average daily dose of acetaminophen, nonsteroidal anti-inflammatory drugs, and aspirin. Information on indications for analgesic use as well as relevant confounders was also gathered prospectively. Compared with women who did not use acetaminophen, the multivariable adjusted relative risk for those who took >500 mg per day was 1.93 (1.30 to 2.88) among older women and 1.99 (1.39 to 2.85) among younger women. For nonsteroidal anti-inflammatory drugs, similar comparisons yielded multivariable relative risks of 1.78 (1.21 to 2.61) among older women and 1.60 (1.10 to 2.32) among younger women. These associations remained significant among women who did not report headache. Aspirin dose was not significantly associated with hypertension. Higher daily doses of acetaminophen and nonsteroidal anti-inflammatory drugs independently increase the risk of hypertension in women. Because acetaminophen and nonsteroidal anti-inflammatory drugs are commonly used, they may contribute to the high prevalence of hypertension in the United States. Journal ISSN: 1524-4563 Issue: 46-3 (2005) Pages: 500-7

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