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Valproate and lorazepam are often used together in the treatment of manic-depressive illness and other psychiatric disorders. This randomized, placebo-controlled, crossover study evaluated the pharmacokinetic and pharmacodynamic interactions between valproate and lorazepam in 16 healthy male volunteers.
The subjects received valproate (500 mg/12 hours) or placebo for the first 12 days and then were crossed over to the other regimen for the following 12 days. During both treatment periods, lorazepam (1 mg/12 hours) was administered on days 6 through 9 and on the morning of day 10.
Concomitant administration of valproate with lorazepam resulted in an 8% increase in steady-state maximum plasma concentrations, a 20% increase in the area under the…