Three Patients Needing High Doses of Valproic Acid to Get Therapeutic Concentrations

Table 3

VPA C/D ratio in Case 2.

Day^1	Formulation	VPA dose^1 (mg/day)	Concentration (μg/mL)	C/D ratio	C/D ratio × 1000^2
All 10 VPA concentrations (C/D ratio × 1000: mean ± SD = 25 ± 5.6, range = 17–33)
8 therapeutic^2 VPA concentrations (C/D ratio × 1000: mean ± SD = 24 ± 5.6, range = 17–33)
5^3	ECDVNa	1500	39	0.026	26
8^3	ECDVNa	1500	49	0.033	33
14^4	ECDVNa	2500	61	0.024	24
20^5	ECDVNa	2500	75	0.030	30
23^6	ECDVNa	2500	82	0.033	33
29^7	ECDVNa	3000	77	0.026	26
36^7	Concentrate	3500	72	0.020	20
41^7	Concentrate	3500	78	0.022	22
48^8	Concentrate	4000	73	0.018	18
55^9	ECDVNa	4000	67	0.017	17

C/D: concentration-to-dose; ECDVNa: enterocoated divalproex sodium; VPA: valproic acid.
¹The Pearson correlation between day of admission and VPA dose was (); VPA dose remained significant in a partial correlation while controlling for VPA concentration: (). This is compatible with a progressive autoinduction indicating, at least with dose range, that it was necessary to increase the dose as the duration lengthened.
²50–125 μg/mL concentrations are considered therapeutic concentrations. As this patient has 2 nontherapeutic concentrations, it would be better to compare a priori with other patients using only the VPA therapeutic concentrations. In reality, eliminating the first 2 VPA concentrations, which were subtherapeutic, made almost no difference.
³Other scheduled oral medications included asenapine 10 mg/day, naproxen 1000 mg/day, omeprazole 20 mg/day, trimethoprim/sulfamethoxazole 1600/320 mg/day (for skin breakdown over swollen lower extremities), and trazodone 100 mg/day.
⁴Other scheduled oral medications included asenapine 15 mg/day, gabapentin 900 mg/day, lisinopril 10 mg/day, meloxicam 15 mg/day, metoprolol 50 mg/day, omeprazole 20 mg/day, trimethoprim/sulfamethoxazole 1600/320 mg/day (for skin breakdown over swollen lower extremities), tramadol 150 mg/day, and trazodone 150 mg/day.
⁵Other scheduled oral medications included asenapine 15 mg/day, gabapentin 900 mg/day, lisinopril 10 mg/day, meloxicam 15 mg/day, metoprolol 50 mg/day, omeprazole 20 mg/day, tramadol 150 mg/day, and trazodone 150 mg/day.
⁶Other scheduled oral medications included asenapine 15 mg/day, furosemide 40 mg/day, gabapentin 900 mg/day, lisinopril 10 mg/day, metoprolol 50 mg/day, omeprazole 20 mg/day, tramadol 150 mg/day, and trazodone 150 mg/day.
⁷Other scheduled oral medications included asenapine 15 mg/day, furosemide 20 mg/day, gabapentin 1200 mg/day, lisinopril 10 mg/day, metoprolol 50 mg/day, omeprazole 20 mg/day, tramadol 200 mg/day, and trazodone 150 mg/day.
⁸Other scheduled oral medications included asenapine 15 mg/day, furosemide 20 mg/day, gabapentin 1200 mg/day, metoprolol 50 mg/day, omeprazole 20 mg/day, tramadol 200 mg/day, and trazodone 150 mg/day.
⁹Other scheduled oral medications included asenapine 15 mg/day, furosemide 20 mg/day, gabapentin 1200 mg/day, metoprolol 50 mg/day, omeprazole 20 mg/day, polyethylene glycol 17 g/day, tramadol 200 mg/day, and trazodone 150 mg/day.