Derivation and evaluation of an equation for prediction of free carbamazepine concentrations in patients comedicated with valproic acid.
The relationship between free carbamazepine fraction (F-CBZ-F) and valproic acid (VPA) was studied in 50 outpatients coming for regular visits to our clinic throughout the day, and was compared with 50 patients without VPA comedication under similar conditions. F-CBZ-F was found to be significantly (t = 3.5, df = 98, p less than 0.001) higher for VPA comedicated patients (0.291 +/- 0.024) when compared with patients without VPA (0.247 +/- 0.016). Linear regression analysis for total plasma VPA concentration versus F-CBZ-F gave the equation: F-CBZ-F = 0.247 + 0.00062 (VPA); n = 50, r = 0.697, p less than 0.001, indicating unreliable prediction of F-CBZ-F from VPA concentration. Substituting the parameter F-CBZ-F by its equivalent (F-CBZ/CBZ) yielded the equation F-CBZ = [0.247 + 0.00062 (VPA)] CBZ. The predictive power of this equation was evaluated by the comparison of obtained and predicted F-CBZ concentrations. An excellent agreement (n = 50, r = 0.981, p less than 0.001) was obtained. Although the empirically derived constants of the equation are not unique and may vary depending on the conditions of different methodologies, the fundamental relationship has been established and can be used to reliably predict F-CBZ concentration from plasma VPA and CBZ concentration.
Haidukewych
D
D
Epilepsy Center of Michigan, Detroit, Michigan 48201.
Zielinski
J J
JJ
Rodin
E A
EA
D000293:Adolescent; D000328:Adult; D002220:Carbamazepine / Q000097:blood*; D002648:Child; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011485:Protein Binding; D014462:Ultrafiltration; D014635:Valproic Acid / Q000009:adverse effects*
D002220:Carbamazepine; D014635:Valproic Acid