A new, large-scale study shows that levalbuterol, a purified form of the widely used asthma medication albuterol, is effective for children in much smaller doses with fewer side effects than the standard medication. Levalbuterol contains only the biologically active right isomer of albuterol. Albuterol’s left isomer is inert, at best, and possibly harmful.
“Albuterol is the most widely prescribed asthma medication for children,” said Henry Milgrom, M.D., senior faculty member at National Jewish Medical and Research Center and lead author of the paper appearing in the December 2001 issue of The Journal of Allergy and Clinical Immunology. “It is valuable to have an alternative to the standard formulation, one that can be especially helpful for patients who use their rescue inhalers several times a day and for acute asthma attacks.”
Most molecules have two mirror-image forms, known as isomers. Although the left and right isomers have the same chemical composition, they are arranged differently, much like a left hand and a right hand. Anyone who has put a left glove on the right hand can imagine how the two isomers of a single compound might interact differently with other molecules. As a result, they can have vastly different biological effects. Thalidomide is the most famous example; one isomer effectively treats morning sickness, while the other can cause horrible birth defects. Hundreds of medications contain both isomers, only one of which is truly therapeutic.
The standard formulation of albuterol, known as racemic albuterol, contains approximately even amounts of both the left and right isomers. It has been known for years that the right isomer generates all the medication’s bronchodilatory effect. The left isomer lingers longer in the body, and animal evidence indicates that it actually increases the “twitchiness” of an asthmatic’s airways. Its effect in humans, however, has been disputed. Racemic albuterol does become less effective at opening airways after frequent, repeated use. In fact, it seems to actually decrease lung function if used too often for too long.
Levalbuterol, marketed by Sepracor Inc. as Xopenex®, has been approved as a bronchodilator for patients 12 and older since March 1999. Dr. Milgrom and his colleagues in the Levalbuterol Pediatric Study Group studied the safety and effectiveness of levalbuterol in children.
For three weeks 319 children ages 4 to 11 all received either a placebo, or one of two doses of levalbuterol or racemic albuterol three times a day. The lowest dose of levalbuterol (0.31 milligrams, half the recommended adult dose) improved lung function more than the recommended dose of racemic albuterol (2.5 milligrams), which is eight times as large and contains four times as much of the active isomer. The levalbuterol took effect more quickly than racemic albuterol and produced fewer side effects. In fact, the low dose of levalbuterol produced heart rates and glucose levels comparable to a placebo.
The researchers also found that a smaller-than-recommended dose of racemic albuterol (1.25 milligrams), which many doctors give to their pediatric patients, produced significant side effects and was less effective than the lowest dose of levalbuterol. Although single-dose experiments have shown similar results, this is the first time that levalbuterol’s advantages in children have been shown in longer trials more reflective of real-world use.
“Many asthma patients do perfectly well on the less expensive racemic albuterol,” said Dr. Milgrom. “But our findings indicate that asthmatic children who use their rescue inhalers several times a day are likely to get more benefits with fewer side effects from levalbuterol. And without a doubt levalbuterol belongs in emergency rooms.”
The research also bolsters the argument that albuterol’s left isomer does indeed have negative effects. Had it been truly inactive, then it should have taken twice as much racemic albuterol, not eight times as much, to produce an equal benefit.
Journal
Journal of Allergy and Clinical Immunology