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

Sodium valproate (CAS 1069-66-5, Epilim(R)) 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 bl ood flow. In recent years, with the aid of SPECT (single photon emission co mputed tomography) and PET (positron emission tomography) it has been shown that marked cerebral blood flow changes occur in epileptic patients. Furth ermore it was established recently that sodium valproate influences the cer ebral blood now in children by decreasing the flow significantly. The prese nt study investigated the effects of sodium valproate on the cerebral blood flow, using Tc-99m-HMPAO (hexamethylpropylene amine oxime) and SPECT, in a primate model, as well as the effects of its drug; interactions with thera peutic agents that influence cerebrovascular dynamics, e.g. sumatriptan, ni modipine and acetazolamide. The current study using single dose treatment w ith sodium valproate did not detect a decrease or increase of the cerebral blood flow when compared with control baseline results. Drug interaction be tween sodium valproate and nimodipine may occur as a reduction of 25 % in c erebral blood flow from the baseline control was observed in this case. The effects observed for the combinations of sodium valproate respectively wit h sumatriptan and acetazolamide are attributed to the influences of the sum atriptan (decrease) and acetazolamide (increase) alone. The cerebral blood flow effects of these drugs and possible interactions during an acute epile ptic seizure need to be investigated.