Midazolam Valproate

Valproate appears to increase the serum levels of diazepam lo-razepam and possibly midazolam, while clobazam appears to raise valproate levels. Clonazepam clearance may increase and valproate clearance decrease during concurrent use, and increased adverse effects have been seen. An isolated case describes sleepwalking in a patient taking valproate and zolpidem. 

An in vitro study in which midazolam was added to serum found that the free fraction of midazolam in the serum from valproate-treated epileptic patients was almost double that found in serum from untreated healthy subjects. It was suggested that displacement of midazolam by valproate could result in an increase in midazolam effects. . dwima/ studies suggest that pre-treatment with valproate may increase the levels of midazolam in the brain. ... 

It seems that valproate reduces the glucuronidation of lorazepam, and therefore benzodiazepines that are mainly metabolised by glucuronide conjugation, such as oxazepam and temazepam are also likely to be affected. It is also thought that valproate may displace midazolam from its... 

Calvo R, Suarez E, Rodriguez-Sasiain JM, Aguilera L. Effect of sodium valproate on midazolam distribution. J Pharm Pharmacol ( 9% S) 40, 150-2. 

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