Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma.

BACKGROUND: Racemic albuterol is an equal mixture of (R)-albuterol (levalbuterol), which is responsible for the bronchodilator effect, and (S)-albuterol, which provides no benefit and may be detrimental. OBJECTIVE: We sought to compare 2 doses of a single enantiomer, levalbuterol (0.63 mg and 1.25 mg), and equivalent amounts of levalbuterol administered as racemic albuterol with placebo in patients with moderate-to-severe asthma. METHODS: This was a randomized, double-blind, parallel-group trial. Three hundred sixty-two patients 12 years of age or older were treated with study drug administered by means of nebulization 3 times daily for 28 days. The primary endpoint was peak change in FEV1 after 4 weeks. RESULTS: The change in peak FEV1 response to the first dose in the combined levalbuterol group was significantly greater compared with the combined racemic albuterol group (0.92 and 0.82 L, respectively; P =.03), with similar but nonsignificant results after 4 weeks (0.84 and 0.74 L, respectively). Improvement in FEV1 was similar for levalbuterol 0.63 mg and racemic albuterol 2.5 mg and greatest for levalbuterol 1.25 mg. Racemic albuterol 1.25 mg demonstrated the weakest bronchodilator effect, particularly after chronic dosing. The greatest increase in FEV1 was seen after levalbuterol 1.25 mg, especially in subjects with severe asthma. All active treatments were well tolerated, and beta-adrenergic side effects after administration of levalbuterol 0.63 mg were reduced relative to levalbuterol 1.25 mg or racemic albuterol 2.5 mg. At week 4, the predose FEV1 value was greatest in patients who received levalbuterol or placebo when compared with those who received racemic albuterol. The difference was more evident and was statistically significant in patients who were not receiving inhaled corticosteroids. CONCLUSION: Levalbuterol appears to provide a better therapeutic index than the standard dose of racemic albuterol. These results support the concept that (S)-albuterol may have detrimental effects on pulmonary function.

Comparison of repeat doses of intramuscular ketorolac tromethamine and morphine sulfate for analgesia after major surgery.

A multicenter, randomized, double-blind, parallel study in 542 patients with moderate or severe postoperative pain compared the analgesic efficacy and safety of intramuscular ketorolac 30 mg (324 patients), morphine 6 mg (110 patients), and morphine 12 mg (108 patients) administered as needed as often as every 2 hours for a maximum of 20 doses or 5 days. The efficacy of ketorolac 30 mg was comparable to that of morphine 12 mg on every efficacy measure (average pain intensity, average pain relief, mean overall medication rating, and percentage of patients withdrawing because of inadequate relief). Ketorolac was statistically superior to morphine 6 mg for average pain intensity and mean overall rating. Ketorolac-treated patients had fewer adverse events than those who received either morphine dose.

Dissociation and diurnal variation of prostaglandin E2 6-keto-prostaglandin-F1-alpha, and thromboxane B2 excretion in healthy females.

The existence of diurnal variation in renal function is well described. Prostaglandins are intimately involved with renal physiology, yet a diurnal variation in their excretion is not well documented. We collected 12 consecutive 2 hour urine specimens from 10 young healthy females and measured prostaglandin E2 [PGE2], thromboxane B2 [TXB2], and 6-keto-prostaglandin-F1-alpha by radioimmunoassay for each specimen. We also measured urine volume, urine sodium, and urine creatinine levels. Regression analysis was used to determine the best sine curve for time versus each set of mean values. Only the urinary excretion of PGE2 and TXB2, as well as water were found to significantly fit the generated sine curves. The curves for PGE2 and TXB2 showed a temporal dissociation in their peak and trough values. The excretion of PGE2 between 0800 hours and 2000 hours was significantly higher than during the hours of 2000 and 0800. The opposite was true for the TXB2 excretion. This data suggests that these two prostaglandins and water are excreted in a sine wave pattern. It also suggests that the excretion of PGE2 and TXB2 may respond to different time associated stimuli. We also showed a significant correlation between PGE2 excretion and both the excretion of water and sodium.