Comparison of pharmacokinetic parameters of valproic acid in seizure-controlled and uncontrolled epileptic patients

Abstract

The purpose of this study was to determine and compare the pharmacokinetic (PK) parameters of valproic acid (VPA) in seizure-controlled and uncontrolled epileptic patients. Pharmacokinetic parameters were estimated for both total and unbound VPA. Forty adults patients were recruited from neurological clinic, Prasat Neurology Institute, Bangkok, 15 patients were in seizure-uncontrolled group and 25 patients were in seizure-controlled group. Pharmacokinetic parameters calculated from total VPA concentrations, demonstrated that the half-life (t[subscript1/2]) of seiazure-uncontrolled group (19.1088+-5.4373 hr) was shorter than 1[subscript1/2] of seizure-controlled group (27.7787+-16.2272 hr) (p=0.142) while the volume of distribution (V[subscriptd]) of seizure-uncontrolled group (0.2546+-0.0880 L/kg) was less extensive when compared to V[subscriptd] of the seizure-controlled group (0.3450+-0.1288 L/kg) (p=0.032). Elimination rate constant (k) of seizure-uncontrolled group (0.0394+-0.0123 hr[superscript-1]) was higher than k of seizure-controlled group (0.0319+-0.0151 hr[superscript-1]) (p=0.142). Clearance (CI) of seizure-uncontrolled group (0.0096+-0.0035 L/hr/kg) was not significantly different from CI of seizure-controlled group (0.0095+-0.0030 L/hr/kg) (p=0.905) Pharmacokinetic parameters obtained from unbound concentrations showed no statistically significant at [alpha] < 0.05 between the seizure-uncontrolled and the seizure-controlled groups due to high variations in PK parameters among patients, higher numbers of subjects were required. However, the same direction as PK of total VPA could be observed, i.e., t[subscript1/2] of the seizure-uncontrolled group (11.2232+-4.8796 hr) was less than t[subscript1/2] of the seizure-controlled group (13.3632+-5.8947 hr) (p=0.234) while the V[subscriptd] of seizure-uncontrolled group (1.3105+-1.1081 L/kg) was smaller as compared to the seizure-controlled group (1.8414+-2.6351 L/kg) (p=0.383) and k of seizure-uncontrolled group (0.0703+-0.0235hr[superscript-1]) was higher than k of seizure-controlled group (0.0616+-0.0275 hr[superscript-1]) (p=0.234). Clearance of seizure-uncontrolled group (0.0796+-0.0621 L/hr/kg) was not different from CI of seizure-controlled group (0.0834+-0.0630 L/hr/kg) (p=0.578) The results provided a more rational understanding of VPA pharmacokinetics in the clinical setting.