Epinephrine protects against severe acute gastric bleeding in rats: role of nitric oxide and glutathione.
Although isosorbide mononitrate was less effective, maternal satisfaction was significantly greater. The safety profile of each agent was such that it would be reasonable to give isosorbide mononitrate, but not prostaglandin E2, on an outpatient basis.
The pharmacokinetic parameters of two oral formulations of 20 mg tablets of isosorbide-5-mononitrate (CAS 16051-77-7, Dilavenil as test and another commercially available preparation as reference) were compared in an open-label, randomized, single oral dose, two-period cross-over design in 20 healthy volunteers under fasting conditions. Plasma concentrations of isosorbide-5-mononitrate were measured by a validated gas chromatographic assay. The parametric 90% confidence intervals of the geometric mean values of the test/reference ratios were 101.2% to 108.5% (point estimate: 104.7%) for AUC0-variation of, 101.6% to 110.7% (point estimate: 106.2%) for AUC0-t, and 98.1% to 115.5% (point estimate: 106.1%) for Cmax, within the acceptance criteria for bioequivalence (80%-125%). Tmax values were analyzed by the nonparametric Wilcoxon test and the difference was not statistically significant. Therefore, it is concluded that the test and reference isosorbide-5-mononitrate formulations are bioequivalent for both the extent and the rate of absorption.
These drugs act upon different variables contributing to portal hypertension and so they may have a powerful synergistic effect in combination. Direct measurement of portal vein flow is a valuable method for assessing the pharmacological modulation of portal venous inflow.
5-IMN proved to be a safe drug when used during the first 48 hours of myocardial infarct even in patients with PCWP < or = 18 mmHg. It improved hemodynamics in all patients especially in those with left ventricular failure.
Both monotherapy with amlodipine and diltiazem (Adizem XL) were effective on symptoms and ambulatory and exercise ischemia. Combination therapy reduced ischemia further, with amlodipine/atenolol superior to diltiazem (Adizem XL)/isosorbide 5-mononitrate. Amlodipine/atenolol was significantly superior during the drug-free interval with maintenance of ischemia reduction.
This study investigated the effects of nitrate on bone mineral density (BMD) and bone marrow perfusion in ovariectomized (OVX) female rats, and also the effects of nitrate on in vitro osteoblastic activity and osteoclastic differentiation of murine monocyte/ macrophage RAW 264.7 cells. Female Sprague-Dawley rats were divided into OVX + nitrate group (isosorbide-5-mononitrate, ISM, 150 mg/kg/ day b.i.d), OVX + vehicle group, and control group. Lumbar spine CT bone densitometry and perfusion MRI were performed on the rats at baseline and week 8 post-OVX. The OVX rats' BMD decreased by 22.5% ± 5.7% at week 8 (p < 0.001); while the OVX + ISM rats' BMD decreased by 13.1% ± 2.7% (p < 0.001). The BMD loss difference between the two groups of rats was significant (p = 0.018). The OVX rats' lumbar vertebral perfusion MRI maximum enhancement (Emax) decreased by 10.3% ± 5.0% at week 8 (p < 0.005), while in OVX + ISM rats, the Emax increased by 5.5% ± 6.9% (p > 0.05). The proliferation of osteoblast-like UMR-106 cells increased significantly with ISM treatment at 0.78 µM to 50 μM. Treatment of UMR-106 cells with ISM also stimulated the BrdU uptake. After the RAW 264.7 cells were co-treated with osteoclastogenesis inducer RANKL and 6.25 μM ~ 100 μM of ISM for 3 days, a trend of dose-dependent increase of osteoclast number was noted.
In volunteers and patients, blood samples for pharmacokinetics were obtained pre-dosing and at intervals for 24 h after dosing.
The clinically used sulfonamide carbonic anhydrase (CA, EC 18.104.22.168) inhibitor dorzolamide (DRZ), a new sulfonamide CA inhibitor also incorporating NO-donating moieties, NCX250, and isosorbide mononitrate (ISMN) (an NO-donating compound with no CA inhibitory properties) were investigated for their intraocular pressure (IOP) lowering effects in rabbits with carbomer-induced glaucoma. NCX250 was more effective than DRZ or ISMN on lowering IOP, increasing ocular hemodynamics, decreasing the inflammatory processes and ocular apoptosis in this animal model of glaucoma. NO participate to the regulation of IOP in glaucoma, having also antiapoptotic and anti-inflammatory effects. The ophthalmic artery, both systolic and diastolic velocities, were significantly reduced in NCX250-treated eyes in comparison to DRZ treated ones, suggesting thus a beneficial effect of NCX250 on the blood supply to the optic nerve. Combining CA inhibition with NO-donating moieties in the same compound offers an excellent approach for the management of glaucoma.
On average, we observed a moderate increase of Q one hour after ISMO dosing (+8.2 +/- 5.4%), but not after placebo (+2.7 +/- 1.6%). This effect of ISMO, which displayed remarkable interindividual variability (95% confidence interval: -3.9%, +20.4%), did not attain statistical significance. D((vein)) and D((art)) were not appreciably affected. No effect was observed three hours after either ISMO or placebo dosing. PP was reduced one hour following ISMO administration, mainly as a function of reduced BP(m), although this variation was not statistically significant. IOP did not change appreciably throughout the duration of the study.