Cerebral blood flow effects of sodium valproate in drug combinations in the baboon model

Sodium valproate (CAS 1069-66-5, Epilim) has been used in the management of epilepsy during the last three decades. Although important information on the pharmacological actions and efficacy of sodium valproate has accrued to date, limited research has been conducted on its effects on cerebral blood flow. In recent years, with the aid of SPECT (single photon emission computed tomography) and PET (positron emission tomography) it has been shown that marked cerebral blood flow changes occur in epileptic patients. Furthermore it was established recently that sodium valproate influences the cerebral blood flow in children by decreasing the flow significantly. The present study investigated the effects of sodium valproate on the cerebral blood flow, using 99mTc-HMPAO (hexamethylpropylene amino oxime) and SPECT, in a primate model, as well as the effects of its drug interactions with therapeutic agents that influence cerebrovascular dynamics, e.g. sumatriptan, nimodipine and acetazolamide. The current study using single dose treatment with sodium valproate did not detect a decrease or increase of the cerebral blood flow when compared with control baseline results. Drug interaction between sodium valproate and nimodipine may occur as a reduction of 25% in cerebral blood flow from the baseline control was observed in this case. The effects observed for the combinations of sodium valproate respectively with sumatriptan and acetazolamide are attributed to the influences of the sumatriptan (decrease) and acetazolamide (increase) alone. The cerebral blood flow effects of these drugs and possible interactions during an acute epileptic seizure need to be investigated.