RELATIONSHIP BETWEEN VALPROIC ACID DOSAGE, PLASMA-CONCENTRATION AND CLEARANCE IN ADULT MONOTHERAPY PATIENTS WITH EPILEPSY

Citation
Be. Gidal et al., RELATIONSHIP BETWEEN VALPROIC ACID DOSAGE, PLASMA-CONCENTRATION AND CLEARANCE IN ADULT MONOTHERAPY PATIENTS WITH EPILEPSY, Journal of clinical pharmacy and therapeutics, 20(4), 1995, pp. 215-219
Citations number
17
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
02694727
Volume
20
Issue
4
Year of publication
1995
Pages
215 - 219
Database
ISI
SICI code
0269-4727(1995)20:4<215:RBVADP>2.0.ZU;2-9
Abstract
Significant variability has been reported in the plasma concentration- dose relationship for the anticonvulsant compound valproic acid (VPA). Several factors may contribute to this observed variability, includin g heterogeneous patient populations of children and adults, polytherap y, and timing of plasma concentration sampling. To optimally determine the relationship between trough VPA plasma concentration and dose, we evaluated a homogeneous group of adult ambulatory patients with epile psy receiving VPA monotherapy. Furthermore, we sought to evaluate whet her a relationship existed between VPA dosage and plasma clearance for both total and unbound or free drug. Steady-state trough plasma conce ntrations were determined in thirty-two patients. Mean VPA dose was 22 .8 +/- 10.3 mg/kg/day. Mean total and unbound VPA plasma concentration s were 97.9 +/- 34.9 and 13.2 +/- 10.6 mu g/ml, respectively, Signific ant correlations between VPA dose and total and unbound plasma concent rations were found (r = 0.82 and r = 0.85, P less than or equal to 0.0 01, respectively). Significant relationships were also observed betwee n VPA dose and clearance. A positive correlation was noted for dose an d total plasma clearance (r = 0.61, P less than or equal to 0.001), wh ile an inverse correlation existed between dose and unbound VPA plasma clearance (r = 0.51, P < 0.01). Although a statistically significant correlation does exist between VPA dosage and both total and unbound p lasma concentrations, significant interpatient variability still remai ns even under 'optimal' therapeutic drug monitoring conditions.