Effect of zaleplon on digoxin pharmacokinetics and pharmacodynamics.

The pharmacokinetics and pharmacodynamics of digoxin alone and digoxin plus zaleplon were studied. Healthy, nonsmoking men between 18 and 45 years of age were given a single oral dose of digoxin 0.375 mg daily on days 1 through 9. On days 10 through 14, the subjects received digoxin 0.375 mg plus oral zaleplon 10 mg daily. Blood samples were obtained on days 3, 5, 8, 9, and 14, and serum digoxin concentration data were analyzed by model-independent pharmacokinetic methods. Blood pressure, heart rate, PR interval, and QTc interval were recorded to determine the effect of zaleplon on digoxin pharmacodynamics. A total of 20 men completed the study. Maximum serum digoxin concentration and area under the serum digoxin concentration-versus-time curve from 0 to 24 hours met bioequivalence test criteria. There were no significant differences in QTc or PR interval between days 9 (digoxin alone) and 14 (digoxin plus zaleplon), and there were no clinically important changes from baseline to the study's end in vital signs, physical examination findings, or ECG results for individual subjects. Eighteen percent of the subjects who received digoxin alone and 35% of those who received digoxin plus zaleplon reported one or more adverse effects; all were mild and resolved quickly. Zaleplon had no significant effects on selected pharmacokinetic and pharmacodynamic properties of digoxin.

Absence of an interaction between ibuprofen and zaleplon.

The potential interaction between zaleplon and ibuprofen was studied. Healthy adult volunteers were given a dose of zaleplon 10 mg alone, a dose of ibuprofen 600 mg alone, or a dose of zaleplon 10 mg and a dose of ibuprofen 600 mg concomitantly in an open-label, randomized, three-period crossover study. There was a seven-day washout period between treatments. Venous blood samples were collected for pharmacokinetic analysis at various intervals up to 14 hours after drug administration. A total of 17 subjects (11 men and 6 women) completed the study. There were no significant differences between zaleplon monotherapy and combination therapy in mean +/- SD, of zaleplon clearance (CL) (2.80 +/- 0.72 versus 2.72 +/- 0.89 L/hr/kg, respectively), maximum plasma concentration (Cmax) (37.1 +/- 17.9 versus 39.8 +/- 20.0 ng/mL), or area under the concentration-versus-time curve (AUC) (56.7 +/- 22.8 versus 59.2 +/- 22.0 ng.hr/mL). There were no significant differences between ibuprofen monotherapy and combination therapy in ibuprofen CL (71.6 +/- 17.0 versus 71.7 +/- 14.9 L/hr/kg), Cmax (40.8 +/- 10.2 versus 40.4 +/- 10.0 micrograms/mL), or AUC (127.6 +/- 29.6 versus 126.4 +/- 29.7 micrograms.hr/mL). Three subjects had one or more adverse effects with zaleplon alone, one subject had one or more with ibuprofen alone, and one subject had one or more with combination therapy. The adverse effects were mild and resolved without intervention. There was no evidence of a significant interaction between zaleplon and ibuprofen.

Comparison of the effects of zaleplon, zolpidem, and triazolam on memory, learning, and psychomotor performance.

Twenty-four healthy male and female subjects, who participated in this randomized, double-blind, crossover study, received single nighttime doses of zaleplon 10 mg (therapeutic dose), zaleplon 20 mg, zolpidem 10 mg (therapeutic dose), zolpidem 20 mg, triazolam 0.25 mg (positive control), and placebo. Subjective behavioral ratings and psychomotor tests were completed before and 1.25 and 8.25 hours after administration of the study drug. The Immediate and Delayed Word Recall tests and the Digit Span Test were used to assess memory. The Digit-Symbol Substitution Test, Paired Associates Learning Test, and Divided Attention Test were used to assess other cognitive skills. Zaleplon 10 mg did not produce any significant changes in memory or learning compared with placebo. All other active treatments, including zolpidem 10 mg, caused psychomotor impairment at the 1.25-hour test battery. Zolpidem 20 mg (twice the therapeutic dose) produced more psychomotor impairment at the 1.25-hour assessment than did any of the other active treatments, including zaleplon 20 mg. At the 8.25-hour time point, test scores for subjects who received zaleplon 10 mg and 20 mg did not differ from the test scores for those who received placebo. However, cognitive impairment persisted up to the 8.25-hour observation for subjects who were administered triazolam 0.25 mg and zolpidem 20 mg. Adverse events associated with the use of zaleplon were transient and mild-to-moderate in severity. Overall, this study shows that zaleplon is a safe hypnotic that does not affect memory, learning, or psychomotor skills associated with vigilance.