Concentrations Of Fenoterol Research Articles

Profiling of cardiac β-adrenoceptor subtypes in the cardiac left ventricle of rats with metabolic syndrome: Comparison with streptozotocin-induced diabetic rats.

Little is known about metabolic syndrome (MetS)-associated cardiomyopathy, especially in relation to the role and contribution of beta-adrenoceptor (β-AR) subtypes. Therefore, we examined the roles of β-AR subtypes in the cardiac function of rats with MetS (MetS group) and compared it with that of rats with streptozotocin (STZ)-induced diabetes (STZ group). Compared with the normal control rats, the protein levels of cardiac β1- and β2-AR in the MetS group were significantly decreased and with no changes in their mRNA levels, whereas the protein levels of β3-AR were similar to those of the controls. However, as shown previously, the protein levels of cardiac β1- and β2-AR in the STZ group were decreased, whereas the β3-AR levels were significantly increased by comparison with the controls. Additionally, the mRNA levels of β2- and β3-AR were increased, but β1-AR mRNA was decreased in the STZ group. Furthermore, left ventricular developed pressure responses to β3-AR agonist BRL37344 were increased in the STZ group but not in the MetS group, whereas for both groups, the responses to noradrenaline were not different from those of the controls. However, the response to stimulation with high concentrations of fenoterol was depressed in the MetS group, compared with the controls, but not in the STZ group. Consequently, our data suggest that the contribution of the β-AR system to cardiac dysfunction in the rats with MetS is not the same as that in the STZ group, although they have similar cardiac dysfunction with similar ultrastructural changes to the myocardium.

Enhanced Bioavailability of Fenoterol Transdermal Systems in Rabbits

The pharmacokinetic and bioavailability of fenoterol, a B 2 adrenergic agonist were studied to determine the feasibility of enhanced transdermal delivery. Fenoterol has been widely used to treat asthmatic patients. Two fenoterol formulations were studied; the first was a liquid formulation of fenoterol in Transcutol: Oleic acid in a ratio 1:1(F1), while the second was a matrix system of fenoterol in Duro-tak ® 87-2074 adhesive with 10% 1-dodecyl-2- pyrrolidinone as an enhancer (F2). For comparison, control matrix with fenoterol without any enhancer (F3) was also tested. The tested formulations were applied to the shaved back skin of rabbits using HILL TOP CHAMBER ® in case of liquid formula. Blood samples were collected via auricle central vein for 24 hours and the plasma concentrations of fenoterol were determined by LC-MS/MS method. Pharmacokinetic parameters were calculated using the WinNonlin computer program. The results showed a maximum concentration of fenoterol in plasma of 514.8 ng/ml after application of the liquid formula while its AUC 0-∞ amounted to be 485972(ng*min/ml) with a dose of 3mg/kg. The transdermal matrix prepared with 10% 1-dodecyl-2-pyrollidinone had a C max of 219 ng/ml and AUC 0-∞ was 124636 (ng*min/ml) which is significantly higher than that obtained after application of the control patch without any enhancer. Therefore, the transdermal systems will offer an efficient drug delivery system for the treatment of bronchial asthma.

The Effects of Fenoterol Inhalation After Acid Aspiration-Induced Lung Injury

Acid aspiration is a serious complication that can occur during general anesthesia. Studies show that beta-agonists have beneficial effects on lung injury. Therefore, we tested the effect of the nebulized beta-agonist fenoterol on lung variables in a rodent model of acid-induced lung injury. In a prospective, randomized, and controlled study, we evaluated the effects of fenoterol inhalation on lung oxygenation, inflammation, and pulmonary histology in a rat model of acid-induced lung injury. Sprague-Dawley rats underwent sevoflurane anesthesia with tracheotomy and carotid catheter insertion. Lung injury was induced by instillation of 0.4 mL/kg 0.1 M hydrochloric acid. The lungs were ventilated for 6 h and randomized to receive either fenoterol inhalation 10 microg or saline inhalation, both at 15 and 180 min after acid aspiration. Mean arterial blood pressures and peak airway pressures were documented, arterial blood gases were determined at 30, 90, 180, 270, and 360 min, and postmortem histology was subsequently examined. Additionally, fenoterol concentrations in bronchoalveolar lavage fluid (BALF) and plasma were determined by liquid chromatography/tandem mass spectroscopy. After 360 min tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were determined in the BALF, and lungs were dried for determination of the wet/dry ratio. Inhalation treatment with 10 microg fenoterol significantly increased oxygenation after 270 and 360 min when compared with placebo. Fenoterol-treated rats showed a significant decrease in IL-6 and TNF-alpha levels and in the wet/dry weight ratio of the lungs. The histologic appearance showed significantly less interstitial edema and leukocyte infiltration in the fenoterol group. The concentration of fenoterol was 10.3 microg/L (median) in the BALF and <1 microg/L in the plasma. Fenoterol inhalation improved oxygenation after 270 and 360 min, attenuated the release of TNF-alpha and IL-6, and diminished the lung edema and infiltration of polymorphonuclear leukocytes.

Compatibility and osmolality of inhaledN-acetylcysteine nebulizing solution with fenoterol and ipratropium

The compatibility, pH, and osmolality of N-acetylcysteine (NAC) nebulizing solution in the presence of ipratropium bromide or fenoterol hydrobromide were studied. Portions (400 microL) of each mixture were sampled immediately upon mixing and one, two, three, four, five, six, and seven hours after mixing and assayed by high-performance liquid chromatography. Osmolality was measured by sampling 100 microL from the filling cup at a five-minute interval during nebulization and by the freezing-point-depression method. Adding NAC solution to fenoterol solution raised the pH from 3.20 to 7.90 and the osmolality to a mean +/- S.D. of 1400.67 +/- 4.51 mOsm/kg. Fenoterol concentrations decreased to 93.71% and NAC concentrations to 92.54% of initial concentrations after seven hours. Mixing ipratropium with NAC solution raised the pH from 3.74 to 7.95 and the osmolality to a mean +/- S.D. of 1413 +/- 11.79 mOsm/kg. The initial ipratropium concentration declined 7.39% and 10.91% one and two hours after mixing with NAC solution, respectively. NAC and ipratropium were stable in nebulizing solution within one hour of mixing. NAC and fenoterol were compatible for at least seven hours.

Fenoterol inhibits superoxide anion generation by human polymorphonuclear leukocytes via β 2-adrenoceptor-dependent and -independent mechanisms

Beta2-adrenoceptor agonists, used widely as bronchodilator in treating bronchial asthma, may have anti-inflammatory activity. We examined whether various widely prescribed beta2-adrenoceptor agonists differ in anti-inflammatory mechanisms. We investigated effects of these drugs on superoxide anion generation by stimulated human polymorphonuclear leukocytes in vitro using chemiluminescence. At high concentrations, fenoterol significantly inhibited both N-formylmethionyl-leucyl-phenylalanine- and phorbol myristate acetate-induced superoxide generation by neutrophils. In contrast, salbutamol or procaterol partially inhibited generation with the former stimulus but not the latter. Inhibition by salbutamol or procaterol was completely reversed by either propranolol, a nonselective beta-adrenoceptor antagonist, or ICI-118551, a beta2-adrenoceptor-selective antagonist. In contrast, the effect of fenoterol at concentrations exceeding 10(-6) M against superoxide generation with the former stimulus was only partially reversed by antagonists, and the effect of high concentrations of fenoterol against generation with the latter stimulus was not reversed. No drugs scavenged superoxide at the highest concentration used (10(-5) M). Fenoterol at high concentrations has an inhibitory effect on superoxide generation that includes a component not mediated via beta2-adrenoceptors. Direct inhibition at or downstream from protein kinase C may be involved.

Determination of fenoterol in human plasma by HPLC with fluorescence detection after derivatization

A new method for the determination of fenoterol is described, which uses HPLC separation with fluorescence detection. Dobutamine is employed as an internal standard. The separation was achieved on a short reversed phase column with a mobile phase consisting of water, acetonitrile and methanol. Prior to chromatography both analytes are derivatized with 9-chloroformyl-carbazole. Isolation of the analytes from plasma is carried out by liquid–liquid extraction into 2-butanol after protein precipitation with acetonitrile. The method is capable of estimating fenoterol concentrations in the sub-nanogram per ml range with sufficient accuracy and precision. The determination of fenoterol can now be carried out in the average laboratory without radiolabelled material.

Kinetic analysis of agonist-induced down-regulation of the beta(2)-adrenergic receptor in BEAS-2B cells reveals high- and low-affinity components.

We examined the interrelationships of internalization and down-regulation of the beta(2)-adrenergic receptor in response to treatment of the BEAS-2B human epithelial cell line with both a series of agonists at high occupancy and with various concentrations of fenoterol that gave occupancies from 0.93 to 0.001. We found that the extent of internalization measured after a 30-min treatment increased as a function of coupling efficiency, with ephedrine, dobutamine, albuterol, fenoterol, and epinephrine giving 0, 7, 17, 48, and 55% internalization, respectively. With the exception of dobutamine, the rates of down-regulation (k(deg)) also showed a dependence on agonist coupling efficiency, giving (in terms of fraction of receptors lost/h) 0.082 with ephedrine, 0.250 with dobutamine, 0.148 with albuterol, 0.194 with fenoterol, and 0.212 with epinephrine. Comparison of down-regulation to internalization showed that weak agonists caused down-regulation in the absence of significant internalization. The extent of internalization caused by fenoterol over a 1000-fold range of occupancy was proportional to agonist occupancy. However, although no internalization was observed with the low concentrations (0.2 and 2 nM fenoterol), these concentrations did cause significant down-regulation. Thus, as with partial agonists, it was clear that down-regulation occurred in the absence of measurable internalization. The kinetics of agonist-induced down-regulation are consistent with a scheme in which down-regulation proceeds by two pathways; a high-affinity, low-capacity component (EC(50) = 0.5 nM) clearly dissociated from internalization and a low-affinity, high-capacity component (EC(50) = 160 nM) closely correlated with internalization.

Facilitatory beta2-adrenoceptors on cholinergic and adrenergic nerve endings of the guinea pig trachea.

Using electrical field stimulation of epithelium-denuded intact guinea pig tracheal tube preparations, we studied the presence and role of prejunctional beta2-adrenoceptors by measuring evoked endogenous acetylcholine (ACh) and norepinephrine (NE) release directly. Analysis of ACh and NE was through two HPLC systems with electrochemical detection. Electrical field stimulation (150 mA, 0.8 ms, 16 Hz, 5 min, biphasic pulses) released 29.1 +/- 2.5 pmol ACh/g tissue and 70.2 +/- 6.2 pmol NE/g tissue. Preincubation for 15 min with the selective beta2-adrenoceptor agonist fenoterol (1 microM) increased both ACh and NE overflow to 178 +/- 28 (P < 0.01) and 165 +/- 12% (P < 0.01), respectively, of control values, increases that were abolished completely by the selective beta2-adrenoceptor antagonist ICI-118551 (1 microM). Further experiments with increasing fenoterol concentrations (0.1-100 microM) and different preincubation periods (1, 5, and 15 min) showed a strong and concentration-dependent facilitation of NE release, with maximum response levels decreasing (from nearly 5-fold to only 2.5-fold of control value) with increasing agonist contact time. In contrast, sensitivity of facilitatory beta2-adrenoceptors on cholinergic nerves to fenoterol gradually increased when the incubation period was prolonged; in addition, a bell-shaped concentration-response relationship was found at 15 min of preincubation. Fenoterol concentration-response relationships (15-min agonist preincubation) in the presence of atropine and yohimbine (1 microM each) were similar in the case of NE release, but in the case of ACh release, the bell shape was lost. The results indicate a differential capacity and response time profile of facilitatory prejunctional beta2-adrenoceptors on adrenergic and cholinergic nerve terminals in the guinea pig trachea and suggest that the receptors on adrenergic nerves are more susceptible to desensitization.

24. Pharmacokinetic and pharmacodynamic of tocolysis by Fenoterol in premature labor

A clinical study of intravenous tocolysis by consecutive infusions is presented. Tocolytic effect, maternal heart rate augmentation and plasma concentrations of Fenoterol are described. Concentration-effect relationship of the side-effect is calculated.

Immunological release of histamine from human lung. I. Studies on the beta 2-sympathomimetic stimulator fenoterol.

Human lung tissue passively sensitized with anti-grass pollen IgE antibodies release histamine upon exposure to specific grass pollen antigen. Fenoterol, a beta 2-sympathomimetic stimulator drug, is shown to be a potent inhibitor of antigen-induced release of histamine. This inhibitory effect occurred with fenoterol concentrations of 2 x 10(-8) to 1 x 10(-7) M, and was determined by 67 and 95%, respectively. Thus, the beta 2-receptor stimulator fenoterol is a valuable drug for treating allergic bronchial asthma since it exhibits a combination of prophylactic and direct therapeutic properties.