Stereoselective metabolism ofRS-albuterol in humans

Walle, Thomas; Eaton, E A; Walle, U K; Pesola, Gene R.

doi:10.1007/bf02772206

Cited by 34 publications

(14 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is due to activation of phospholipan and increased phosphatidyl-inositol turnover with increased inositol triphosphate (1,4,5), IP 3 , levels (41)(42)(43)(44). Exposure to the S-enantiomer in these preparations causes heightened responsiveness to airway spasmogens including histamine and leukotriene C 4 and has a proinflammatory effect on eosinophil superoxide production in response to interleukin-5 (43).…”

Section: Discussionmentioning

confidence: 99%

A prospective randomized controlled blinded study of three bronchodilators in infants with respiratory syncytial virus bronchiolitis on mechanical ventilation*

Levin

Garg

Hall

et al. 2008

Pediatric Critical Care Medicine

View full text Add to dashboard Cite

Similar statistically significant bronchodilation occurred after all three bronchodilators as indicated by a decrease in peak inspiratory pressure and respiratory system resistance, but these changes were small and probably clinically insignificant. However, side effects of bronchodilators, such as tachycardia, also occurred, and these may be clinically significant. Thus the benefit of bronchodilator treatment in these patients is small, does not differ among the drugs we studied and of questionable value.

show abstract

Section: Discussionmentioning

confidence: 99%

A prospective randomized controlled blinded study of three bronchodilators in infants with respiratory syncytial virus bronchiolitis on mechanical ventilation*

Levin

Garg

Hall

et al. 2008

Pediatric Critical Care Medicine

View full text Add to dashboard Cite

show abstract

“…Over time, plasma concentrations of (S)-albuterol remain many-fold higher than levalbuterol. Several studies have documented that (R)-albuterol is a more natural substrate for the metabolic arylsulfatase enzymes, and therefore is more rapidly eliminated than (S)-albuterol [31,32]. Thus, the maximum concentration and the area under the curve (AUC) for (S)-albuterol are four times higher than those of (R)-albuterol, and the elimination half-life of (S)-albuterol is approximately 50% longer than that of (R)-albuterol [30,[33][34][35].…”

Section: Pharmacokinetic Characteristicsmentioning

confidence: 99%

Single-isomer levalbuterol: A review of the acute data

Nowak

2003

Curr Allergy Asthma Rep

View full text Add to dashboard Cite

Levalbuterol, the pure (R)-isomer of racemic albuterol, is a new therapeutic option for patients with asthma. Racemic albuterol comprises a 50:50 mixture of (R)- and (S)-albuterol, with (R)-albuterol conferring all of the bronchodilator effects of the racemate. Numerous preclinical and in vitro studies have indicated that (S)-albuterol is not an inert isomer, but may have proinflammatory effects. Results from clinical trials in adults and children with asthma have demonstrated that 0.63 mg levalbuterol provides effective bronchodilation with lower b-mediated side effects compared with 2.5 mg racemic albuterol. In the emergency department, levalbuterol provided greater bronchodilation and significantly reduced hospital admissions compared with racemic albuterol. Recent studies have supported that levalbuterol use in acute settings may reduce the cost of asthma treatment by decreasing the total treatments and subsequent respiratory therapy resources. Levalbuterol provides heath care professionals with a safe, effective, and potentially cost-saving alternative to racemic albuterol for the treatment of patients with asthma.

show abstract

“…(S)-Albuterol induces paradoxical reactions in airways and may decrease asthma control, although the mechanism whereby (S)-albuterol evokes hyperresponsiveness appears to be unrelated to β 2 -adrenoceptor activation [6, 9]. Furthermore, the metabolic clearance rate for (S)-albuterol is tenfold slower than that for (R)-albuterol [10, 11], which may result in accumulation of (S)-albuterol and subsequent potential adverse effects in asthma control. Specifically, (S)-albuterol increases intracellular calcium [12], enhances experimental airway hyperresponsiveness to spasmogens [13], and may have proinflammatory effects as demonstrated by eosinophil superoxide production in response to interleukin (IL-5) [14].…”

Section: Introductionmentioning

confidence: 99%

(S)-Albuterol Increases the Production of Histamine and IL-4 in Mast Cells

Cho

Hartleroad

2001

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Background: Racemic albuterol is an equimolar mixture of (R)-albuterol and (S)-albuterol. Previous studies indicated that (S)-albuterol may exert proinflammatory effects. We investigated the effect of (S)-albuterol in the production of mast cell mediators such as histamine and interleukin (IL)-4. Methods: Murine mast cells were either unstimulated or stimulated by IgE-receptor crosslinking. Both groups of mast cells were pretreated with either (R)- or (S)-albuterol. Histamine release and IL-4 secretion were measured by ELISA. Expression of L-histidine decarboxylase (L-HDC) and IL-4 was analyzed by semiquantitative reverse transcription-polymerase chain re- action. Results: In the overnight IgE-stimulated group, secreted histamine and total histamine were approximately 19.9 and 18.3% greater in cells co-treated with (S)-albuterol than untreated cells, respectively (n = 4, p < 0.002, p < 0.02), whereas there was no significant difference between the cells treated with (R)-albuterol and untreated cells. When the IgE-stimulated cells were treated with (S)-albuterol for 6 and 24 h, histamine release was approximately 18.3 and 24% greater, respectively (n = 4, p < 0.01). L-HDC is an essential enzyme for synthesizing histamine and its message was significantly induced in mast cells treated with (S)-albuterol. Both IL-4 message and protein were also significantly increased after treatment with (S)-albuterol. In the overnight IgE-stimulated group, IL-4 secretion was increased by approximately 58.8% upon exposure to (S)-albuterol (n = 5, p < 0.01). (R)-albuterol had no effect on mast cell mediator release. Conclusion: (S)-albuterol may have adverse effects in asthma control by activating mast cells to produce inflammatory mediators such as histamine and IL-4.

show abstract

Stereoselective metabolism ofRS-albuterol in humans

Cited by 34 publications

References 32 publications

A prospective randomized controlled blinded study of three bronchodilators in infants with respiratory syncytial virus bronchiolitis on mechanical ventilation*

A prospective randomized controlled blinded study of three bronchodilators in infants with respiratory syncytial virus bronchiolitis on mechanical ventilation*

Single-isomer levalbuterol: A review of the acute data

(S)-Albuterol Increases the Production of Histamine and IL-4 in Mast Cells

Contact Info

Product

Resources

About