Apparent clearance of valproic acid in elderly epileptic patients: estimation of the confounding effect of albumin concentration

Figures & data

Table I. Pharmacokinetic and biochemical variables according to age in epileptic patients treated in monotherapy with valproic acid.

	≤19 years	20–64 years	≥65 years
n (males/females)	24 (14/10)	57 (29/38)	21 (10/11)
Age (years)	13.7 ± 0.9 (15.0)	37.9 ± 1.6 (38.0)	76.9 ± 1.7 (76.0)
VPA dose (mg/day)	836.7 ± 91.0 (800.0)***	1208.8 ± 52.5 (1200.0)	1066.7 ± 70.3 (1000.0)
VPA Css (μg/mL)	66.4 ± 4.6 (67.5)	67.9 ± 2.3 (68.9)	60.4 ± 4.3 (54.4)
VPA CL (mL/min)	9.2 ± 0.8 (8.8)***	12.7 ± 0.6 (11.7)	13.9 ± 2.0 (11.45)
VPA α (%)	5.87 ± 0.13 (5.6)*	6.59 ± 0.21 (6.2)	9.92 ± 1.09 (8.5)****
VPA CssN (μg/mL)	76.2 ± 9.7 (59.0)	96.7 ± 10.4 (67.9)	145.3 ± 27.7 (71.1)
VPA CLN (mL/min)	9.3 ± 0.9 (10.0)	11.4 ± 0.8 (11.1)	8.1 ± 0.9 (6.7)**
Albumin (g/L)	44.2 ± 1.0 (45.0)*	43.1 ± 1.0 (43.0)	37.0 ± 1.1 (38.0)****
AST (U/L)	14.7 ± 0.7 (14.5)	15.0 ± 1.1 (14.0)	17.6 ± 3.4 (13.0)
ALT (U/L)	14.9 ± 2.3 (12.0)*	19.9 ± 2.0 (15.0)	17.3 ± 3.7 (13.0)
GGT (U/L)	12.7 ± 3.1 (8.5)	17.0 ± 1.9 (12.0)	25.7 ± 6.8 (13.0)
APRI score	0.28 ± 0.02 (0.24)	0.33 ± 0.03 (0.28)	0.48 ± 0.12 (0.31)
AST/ALT ratio	1.2 ± 0.1 (1.2)****	0.9 ± 0.1 (0.7)	1.1 ± 0.1 (1.0)***
GFR (mL/min/1.73 m^2)	144.0 ± 3.1 (144.2)****	102.4 ± 2.6 (102.8)	73.2 ± 4.0 (79.2)****

Statistical significance against non-elderly adult patients (20–64 years): *P < 0.05, **P < 0.01, ***P < 0.005, ****P < 0.001.

Results are expressed as mean ± SEM (median).

Figure 1. Relationship between total (Css) and albumin normalized total (Css_N) concentrations of valproic acid in epileptic patients of <65 (○) and ≥65 (•) years of age. The dashed lines correspond to the limits of the valproic acid therapeutic range (50–100 μg/mL).