DECREASED PLASMA-PROTEIN BINDING OF VALPROATE IN PATIENTS WITH ACUTE HEAD TRAUMA

1 One hundred and ten plasma samples were obtained from 50 patients tr eated with valproate for prophylaxis of post-traumatic head injuries. The samples were selected to include a wide range of albumin concentra tions and were assayed for free and total valproate concentrations. Va lproate binding parameters were determined from the Scatchard equation for one binding site using reweighted least squares analysis. 2 Plasm a albumin concentrations were measured in 130 patients with head traum a. They started to decrease immediately after trauma, reaching a minim um at 5-7 days of approximately 24% of baseline value and did not retu rn to normal until 1 month. 3 The free fraction of valproate varied si x to seven-fold as albumin concentration ranged from 1.5 to 4.8 g 100 ml(-1) (218-696 mu mol 1(-1)). The mean association constant for bindi ng (K-a) was 0.008 mu mol 1(-1) and the mean number of binding sites ( N) was 2.0. There values were similar to those reported for valproate in otherwise healthy patients with epilepsy. 4 Because of saturable pr otein binding of valproate, hypoalbuminaemia may necessitate the monit oring of free valproate concentrations to avoid toxicity when valproat e is used in patients with acute head injury.