Pharmacology - Valproic acid (Sodium Valproate) and Lorazepam

[tyranny4u]

SWIM read that valproic acid will double the effect of Lorazepam.
So if you take both substances you might have to talk only half the dose of Lorazepam.

[Jatelka]

Sodium valproate is a liver enzyme inhibitor, and as such, will reduce clearance of Lorazepam, theoretically increasing plasma concentration levels

See this abstract:

Effect of valproate on the pharmacokinetics and pharmacodynamics of lorazepam.
Journal of Clinical Pharmacology 1997 May;37(5):442-50
Samara EE, Granneman RG, Witt GF, Cavanaugh JH

"The pharmacokinetic-pharmacodynamic interaction between valproate and lorazepam was evaluated in this randomized, double-blind, placebo-controlled crossover study. Sixteen healthy male volunteers enrolled in the study to receive either divalproex sodium (500 mg every 12 hours) or matching placebo for 12 days in the first period, and then to receive the other regimen for an identical second 12-day period. In both periods, lorazepam (1 mg every 12 hours) was administered on days 6 through 9 and on the morning of day 10. Concomitant administration of divalproex sodium with lorazepam resulted in an 8%, 20%, and 31% increase in steady-state maximum plasma concentration, area under the concentration-time curve, and trough plasma concentrations of lorazepam, respectively. The apparent clearance of lorazepam through the formation of lorazepam glucuronide was reduced by 31% during coadministration of divalproex sodium. Pharmacokinetic properties of valproate did not change significantly in the ten available participants during coadministration of lorazepam. Sedation scales revealed no statistically significant differences in sedation between the two regimens. It is concluded that valproate increases plasma concentrations and reduces clearance of lorazepam, most likely by impairing hepatic glucuronidation, and that coadministration of lorazepam does not affect the steady-state"

But please also see this:

Coma probably induced by lorazepam-valproate interaction
Seizure 2002 Mar;11(2):124-5
Lee SA, Lee JK, Heo K

"Both valproate (VPA) and lorazepam (LZP) are primarily cleared from the body by glucuronidation. Concomitant administration of VPA has been reported to reduce the elimination of LZP. However, it remains unknown whether this drug interaction is clinically significant. We report a patient with epilepsy who showed that VPA-LZP interaction could result in severe encephalopathy such as coma."