Topical use of nitroglycerin for anal fissures by nursing mothers appears to have no adverse effects on their breastfed infants. Topical use on the nipples has been used for alleviation of Raynaud phenomenon of the nipples, but only after cessation of breastfeeding.[1] Nitroglycerin should not be used topically on the nipples during breastfeeding. Sublingual and intravenous nitroglycerin have not been studied during breastfeeding. Observe infants for flushing and discomfort after breastfeeding.

The effect of exogenous nitric oxide donor deponit-10 (nitroglycerin) on red cell indices in the offspring of rats with experimental disturbances of uteroplacental circulation has been investigated. It is established that fetal hypoxia facilitates the mobilization of functional reserves of the red cell system in the prenatal and early days of postnatal life of offspring in white rats, which is manifested by the growing process of erythropoiesis. Hyperfunction of the erythrocyte system in the first lifedays of pups leads eventually to a depletion of its functional capacities. The administration of an exogenous nitric oxide donor on the background of damaged uteroplacental circulation prevents the depletion and disruption of the functional reserves of the blood red cell system.

The purpose of paper is an estimation of morphometric parameters and status of NO-dependent mechanisms of embryos placenta of white rats in normal conditions, experimental disturbance of the utero-placental circulation and after the nitric oxide donator "Deponit-10" using. The volume density of blood vessels in the placenta and placental vascular exchange area significantly increases under chronic intrauterine hypoxia. The donator of nitric oxide has a positive effect on morphometric parameters of the placenta, provides effective adaptation of feto-placental blood flow to hypoxia and could be useful for clinical practice.

The KBS-3 underground nuclear waste repository concept designed by the Swedish Nuclear Fuel and Waste Management Co. (SKB) includes a bentonite buffer barrier surrounding the copper canisters and the iron insert where spent nuclear fuel will be placed. Bentonite is also part of the backfill material used to seal the access and deposition tunnels of the repository. The bentonite barrier has three main safety functions: to ensure the physical stability of the canister, to retard the intrusion of groundwater to the canisters, and in case of canister failure, to retard the migration of radionuclides to the geosphere. Laboratory experiments (< 10 years long) have provided evidence of the control exerted by accessory minerals and clay surfaces on the pore water chemistry. The evolution of the pore water chemistry will be a primordial factor on the long-term stability of the bentonite barrier, which is a key issue in the safety assessments of the KBS-3 concept. In this work we aim to study the long-term geochemical evolution of bentonite and its pore water in the evolving geochemical environment due to climate change. In order to do this, reactive transport simulations are used to predict the interaction between groundwater and bentonite which is simulated following two different pathways: (1) groundwater flow through the backfill in the deposition tunnels, eventually reaching the top of the deposition hole, and (2) direct connection between groundwater and bentonite rings through fractures in the granite crosscutting the deposition hole. The influence of changes in climate has been tested using three different waters interacting with the bentonite: present-day groundwater, water derived from ice melting, and deep-seated brine. Two commercial bentonites have been considered as buffer material, MX-80 and Deponit CA-N, and one natural clay (Friedland type) for the backfill. They show differences in the composition of the exchangeable cations and in the accessory mineral content. Results from the simulations indicate that pore water chemistry is controlled by the equilibrium with the accessory minerals, especially carbonates. pH is buffered by precipitation/dissolution of calcite and dolomite, when present. The equilibrium of these minerals is deeply influenced by gypsum dissolution and cation exchange reactions in the smectite interlayer. If carbonate minerals are initially absent in bentonite, pH is then controlled by surface acidity reactions in the hydroxyl groups at the edge sites of the clay fraction, although its buffering capacity is not as strong as the equilibrium with carbonate minerals. The redox capacity of the bentonite pore water system is mainly controlled by Fe(II)-bearing minerals (pyrite and siderite). Changes in the groundwater composition lead to variations in the cation exchange occupancy, and dissolution-precipitation of carbonate minerals and gypsum. The most significant changes in the evolution of the system are predicted when ice-melting water, which is highly diluted and alkaline, enters into the system. In this case, the dissolution of carbonate minerals is enhanced, increasing pH in the bentonite pore water. Moreover, a rapid change in the population of exchange sites in the smectite is expected due to the replacement of Na for Ca.

The patch performances and the success of the transdermal drug delivery can be significantly affected by the quality of contact between the patch and the skin. Poor adhesion will dramatically reduce percutaneous delivery. In this study the adhesive properties (peel force and creep resistance) of three monolayer self-adhesive nitroglycerin (NTG) patches available on the market, Deponit, Minitran, and Triniplas, were compared. The patches were characterized also in terms of in vitro drug release and ex vivo skin permeation. The creep resistance values verified in the case of Deponit and Triniplas indicated a low cohesion of these matrices. The peel force values were in the accepted range, even if Triniplas and Deponit showed values double that shown by Minitran. The percentage of NTG released in vitro after two hours in all cases exceeded ninety percent. The ex vivo permeation profiles were similar, even if the three patches had different loaded amounts and surface areas. The measured permeated amount, 11 mg permeated in 24 h, was predictive of the claimed in vivo release (10 mg in 24 h).

In the course of this study both the bioavailability and main pharmacokinetic parameters of the glyceryl trinitrate (GTN, CAS 55-63-0) metabolites 1,2 and 1,3-glyceryl dinitrate (1,2-GDN and 1,3-GDN) were to be determined following transdermal application of a glyceryl trinitrate test patch (Deponit 5) and an already marketed reference patch. For this purpose, both patches were examined in healthy volunteers according to a randomized two-way cross-over design, blood samples were withdrawn up to 15 h after start of patch application and the plasma concentrations of both metabolites were quantified using a GC/MS method. The investigation showed the following results: Metabolite 1,2-glyceryl dinitrate: For the area under the curve from time 0 to the last quantifiable sample (AUC(0-Tlast) arithmetic mean values of 23.77 h.ng/ml (test patch) and 27.83 h.ng/ml (reference patch) were found. The corresponding peak plasma levels were 2.45 ng/ml and 2.93 ng/ml, respectively; they were reached after 6.4 h (test patch) and 8.31 h (reference patch). Metabolite 1,3-glyceryl dinitrate: The arithmetic mean values for AUC(0-Tlast) were 3.32 h.ng/ml (test patch) and 3.81 h.ng/ml (reference patch). The maximum plasma levels were 0.35 ng/ml and 0.41 ng/ml for the test and reference preparation, reached after 6.4 h and after 7.86 h, respectively. The statistical comparison (ANOVA, confidence intervals) showed bioequivalence between both patches concerning the metabolites investigated. The typical side effects known after nitrate therapy also occurred in the course of this study.

The study objective was to determine the bioavailability and main pharmacokinetic parameters of glyceryl trinitrate (GTN, CAS 55-63-0) following cutaneous application of two different glyceryl trinitrate patches using a randomized cross-over design. The two patches investigated were Deponit 5 (a newly developed test patch) and an already marketed reference patch. Thirty-seven healthy male volunteers were included in this study; 36 of them completed the investigation. Blood samples were withdrawn up to 15 h after start of patch application and plasma concentrations of glyceryl trinitrate were quantified by a GC/MS method. For the areas under the curve from time 0 to the last quantifiable sample, AUC(O-Tlast), mean values of 1545 (test patch, n = 35) and 1686 h.pg/ml (reference patch, n = 35) were found. The corresponding peak glyceryl trinitrate plasma levels were 253 and 263 pg/ml, respectively; they were reached after 6.58 h (test patch) and 7.72 h (reference patch). The statistical comparison (ANOVA, confidence intervals) of the pharmacokinetic parameters found in the study resulted in bioequivalence of both patches. Typical side-effects known and described under glyceryl trinitrate therapy were also observed in this study.

We studied the long-term antianginal and anti-ischemic effects of two dosage regimens designed to prevent tolerance to transdermal nitroglycerin (TNTG): (1) 10 mg TNTG applied for 16 h with a 'nitrate-free' interval of 8 h; (2) 10 mg TNTG applied for 16 h followed by a 'nitrate-low' interval of 5 mg applied for 8 h. 129 patients completing a 3-month study period were evaluated by repeated exercise tests. Both regimens significantly increased maximum exercise duration at 3 months, from 699.1 +/- 23.4 to 833 +/- 21.9 s and from 686.1 +/- 20 to 789.6 +/- 22.6 s, respectively, reduced the number of patients with 1 mm S-T segment depression and increased the time duration to 1 mm S-T segment depression. Marked reductions in anginal attacks was observed in both groups: from 6.5 to 0.15 attacks per week and from 6.0 to 0.15 attacks per week, respectively. No statistically significant differences were found between the groups, and both regimens were well tolerated. In conclusion, our results demonstrate sustained antianginal efficacy, without tolerance, of either 'nitrate-free' of 'nitrate-low' interval therapy with transdermal nitroglycerin.

Transdermal nitroglycerin patches are used mainly in the therapy of angina pectoris. However, the magnitude and duration of their effects are still controversial. In this study, transdermal discs with nitroglycerin were given to 14 patients with acute myocardial infarction (AMI) and mild hemodynamic impairment. Seven patients received Nitroderm TTS, and seven patients Deponit 5 (in this case 2 patches), the nitroglycerin dose being 10 mg. Hemodynamic measurements were made 19-24 h after application of the patch and 1 h after its removal. Comparing with the values obtained 1 h after removal of the patch, 19-24 h after the application of the patch heart rate was significantly higher (90.2 +/- 3.8 vs. 85.6 +/- 4.0 min-1; p less than 0.01), mean right atrial pressure was significantly lower (10.8 +/- 1.0 vs. 12.7 +/- 1.3 mm Hg; p less than 0.01), and so were the pulmonary artery pressure: systolic (36.9 +/- 3.0 vs. 43.0 +/- 3.1 mm Hg; p less than 0.001), mean (26.8 +/- 2.1 vs. 31.4 +/- 2.0 mm Hg; p less than 0.001) and the capillary wedge pressure (19.2 +/- 1.8 vs. 23.0 +/- 1.9 mm Hg; p less than 0.01). These findings revealed that in patients with AMI hemodynamic effects persist for at least 19 h after single application of a nitroglycerin patch of 10 mg. The therapy is safe and the risk of side effects is small.

One hundred forty-two patients with stable angina were enrolled in a four-week, multicenter, office-based study to compare the adhesion properties, patient preference, and tolerability of two commercially available transdermal nitroglycerin patches. Data from 139 patients were analyzed. Each patient simultaneously wore one 5-mg Transderm-Nitro (TDN) patch and one 5-mg Deponit (DPT) patch. Patients daily recorded the following information in a diary format: number of angina attacks, frequency of sublingual nitroglycerin use, patch adhesion, and problems at the adhesion site or other medical problems. At the end of the study, patients rated their patch preferences based on ease of application and removal, ease of removing backing, overall adhesion, and adhesion under specific conditions, such as showering, swimming, exercise, hot weather, high humidity, and perspiration. They also specified which patch they would choose for their next prescription. Differences in adhesion properties (P less than 0.0001) and tolerability at the site of application favored TDN over DPT. In addition, significantly more patients (P less than 0.0001) specified TDN as their next prescription choice (83% vs 11%).

A randomized two-period crossover trial was carried out to compare the efficacy, tolerability and patient acceptability of two transdermal ('patch') formulations of glyceryl trinitrate. 'Deponit' 5 and 'Transiderm-Nitro' 5, both designed to deliver 5 mg glyceryl trinitrate in 24 hours. All patients were treated for 4 weeks with each of the formulations, changed once per day. Forty-seven patients entered the trial and all completed both phases of treatment. Both drugs resulted in highly significant mean reductions in angina attack frequency, the reduction being significantly greater with 'Deponit'. Similarly, mean sublingual glyceryl trinitrate consumption was also reduced; again, the greater reduction with 'Deponit' was significant. In terms of effectiveness, 'Deponit' was preferred to 'Transiderm-Nitro' by 19 patients, whilst only 5 patients preferred 'Transiderm-Nitro' (p less than 0.01). In terms of ease of application, comfort, appearance and adhesion (assessed in relation to daytime, night-time, washing, bathing and exercising), there were no appreciable or significant differences between patients' assessments of the two forms. Neither treatment had any appreciable effect on heart rate or blood pressure. Both formulations were very well tolerated, with very few reported side-effects.

In this double-blind randomized placebo-controlled crossover study, the antianginal and anti-ischemic effect of a new transdermal system, releasing 10 mg of nitroglycerin (NTG) over 24 hours, was assessed in 19 outpatients with stable exercise-induced angina pectoris. The trial consisted of a 3-day washout: a 1-week period with verum or placebo patch followed by a second 1-week period with the other patch. During the study only sublingual NTG was allowed, and its consumption and the number of attacks recorded. Treadmill exercise tests were performed at the end of washout before patch application (baseline test) and 3 and 24 hours, respectively, after each period of 7 days of application of 1 patch daily. Systolic blood pressure and heart rate did not vary significantly at rest in the 17 patients who completed the trial. Angina was reduced 31.3% and NTG consumption 34.3% (p less than 0.01) during the week with Deponit 10 as compared with placebo. Exercise duration increased 29 and 16.1% (p less than 0.001 and p less than 0.1, respectively) at 3 and 24 hours with a verum patch as compared with placebo. ST-segment depression at comparable loads decreased 69 and 40.5% (p less than 0.01) at 3 and 24 hours, respectively, after application of Deponit. Onset of angina was delayed and maximal heart rate-blood pressure product significantly increased at 3 and 24 hours of treatment. It is concluded that Deponit 10 patch is effective in reducing anginal attacks and in increasing exercise capacity up to 24 hours after application.

Because silent ischemia is not associated with an increase in heart rate and, being asymptomatic, its treatment requires constant therapeutic plasma levels of the drug used, a transdermal nitroglycerin patch (Deponit) was selected for treatment of this condition. Eight patients with documented silent ischemia were studied. All patients also had angina on effort treated with calcium antagonists (n = 8) and beta blockers (n = 6). They were evaluated by 24-hour ambulatory electrocardiographic monitoring. The transdermal nitroglycerin patch, 20 to 30 mg/24 hours, reduced the number of silent ischemic episodes from 9.25 +/- 5.52 to 2.4 +/- 2.0 episodes per 24 hours (p less than 0.001). The maximal ST-segment depression was reduced from 3.1 +/- 0.7 to 0.9 +/- 0.7 mm (p less than 0.001). Ventricular premature beats were significantly reduced, by 50%. Symptomatic ischemic episodes were completely suppressed. Thus, transdermal nitroglycerin, in moderate doses, is effective in suppressing silent ischemia in patients with angina pectoris who have silent ischemic episodes despite treatment with other antianginal agents.

The haemodynamic effect of transdermal nitroglycerin treatment with Deponit 10 was investigated in 10 patients with chronic cardiac failure due to coronary artery disease (8 patients) or congestive cardiomyopathy (2 patients). The patients had elevated mean pulmonary artery (PA) and pulmonary capillary wedge pressures (PC) at rest (32.1 +/- 5.9 and 24.1 +/- 6.6 mm Hg). Heart rate (87 +/- 10), arterial blood pressure (133 +/- 20/77 +/- 8 mm Hg) and cardiac index (3.73 +/- 0.85 l/min/m2) were in the normal range. During treatment with Deponit 10 mean PA and PC pressures decreased significantly (p less than 0.01) to 25.5 +/- 6.3 and 18.1 +/- 6.4 mm Hg, respectively. The effect was seen within 1 hour after application of the transdermal therapeutic system and reached its nadir after 2 hours. PA and PC pressures remained significantly below control for 12-16 hours. Heart rate, arterial blood pressure and cardiac index were not changed. After removal of the patch 4 patients showed a rebound haemodynamic deterioration. Their mean PA pressure rose by more than 4 mm Hg above the respective control values. These patients had the highest control PA pressures of the group studied (37.5 +/- 2.4 mm Hg). Thus, transdermal nitroglycerin treatment with Deponit 10 reduces cardiac preload in patients with congestive heart failure for 12-16 hours, whereas cardiac afterload remains unaffected. After removal of the patch a rebound phenomenon can occur especially in patients with severe cardiac failure.