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

Table 2

VPA C/D ratio in Case 1.

Day	VPA dose (mg/day)	Concentration (g/mL)	C/D ratio	C/D ratio × 1000
Valproic acid concentrate (C/D ratio × 1000: mean ± SD = 15^1  ± 2.6, range = 10–21)
7^3	5250	54	0.010	10
14^4	5250	68	0.013	13
21^5	5250	68	0.013	13
29^5	5250	76	0.014	14
70^5	5250	59	0.011	11
98^6	5250	66	0.013	13
119^6	5250	85	0.016	16
126^6	5250	61	0.012	12
140^6	5250	75	0.014	14
175^6	5250	79	0.015	15
188^6	5250	64	0.012	12
202^7	5250	64	0.012	12
238^8	5250	88	0.017	17
252^8	5250	110	0.021	21
260^9	5250	86	0.016	16
280^9	5250	92	0.018	18
287^9	5250	87	0.017	17
301^10	5250	87	0.017	17
319^10	5250	92	0.018	18
350^10	5250	99	0.019	19
378^11	5250	85	0.016	16
420^12	5250	91	0.017	17
427^12	5250	97	0.018	18
434^12	5250	87	0.017	17
470^12	5250	87	0.017	17
498^13	5250	90	0.017	17
552^13	5250	95	0.018	18
582^13	5250	81	0.015	15
609^13	5250	88	0.017	17
637^7	5250	80	0.015	15
928^14	5250	111	0.021	21
945^15	5250	93	0.018	18
978^16	5250	78	0.015	15
998^17	5250	67	0.013	13
1026^18	5250	67	0.013	13
1054^19	5250	66	0.013	13
1082^19	5250	71	0.014	14
1110^19	5250	63	0.012	12
1145^20	5250	69	0.013	13
1166^21	5250	93	0.018	18
1202^22	5250	89	0.017	17
1208^23	5250	75	0.014	14
1236^24	5250	88	0.017	17
1251^25	5250	87	0.017	17
EC divalproex sodium (C/D ratio × 1000: mean ± SD = 39^1  ± 6.3, range = 28–48)
1306^25	5250	145^2	0.028	28
1320^25	3750	135	0.036	36
1334^25	3000	127	0.042	42
1373^25	2500	120	0.048	48
1348^25	2000	73	0.037	37
1362^25	2000	82	0.041	41
1376^25	2000	78	0.039	39

C/D: concentration-to-dose; EC: enterocoated; VPA: valproic acid.
¹According to an independent -test calculated with equal variance not assumed, there was significant difference (; df = 6.3, ) between these two means, 15 in VPA concentrate and 39 in divalproex sodium.
²This VPA concentration was measured 4 weeks after switching from VPA concentrate to divalproex sodium. With a high VPA concentration at that time, the patient showed increased drowsiness.
³Other scheduled oral medications included benztropine 3 mg/day, gemfibrozil 1200 mg/day, propranolol 80 mg/day, and quetiapine 700 mg/day.
⁴Other scheduled oral medications included benztropine 3 mg/day, gemfibrozil 1200 mg/day, olanzapine 5 mg/day, propranolol 80 mg/day, and quetiapine 500 mg/day.
⁵Other scheduled oral medications included benztropine 3 mg/day, gemfibrozil 1200 mg/day, olanzapine 5 mg/day, and propranolol 80 mg/day.
⁶Other scheduled oral medications included benztropine 4 mg/day, gemfibrozil 1200 mg/day, olanzapine 5 mg/day, and propranolol 80 mg/day.
⁷Other scheduled oral medications included benztropine 4 mg/day, gemfibrozil 1200 mg/day, olanzapine 5 mg/day, and propranolol 60 mg/day.
⁸Other scheduled oral medications included benztropine 4 mg/day, gemfibrozil 1200 mg/day, olanzapine 2.5 mg/day, and propranolol 30 mg/day.
⁹Other scheduled oral medications included benztropine 4 mg/day, gemfibrozil 1200 mg/day, olanzapine 2.5 mg/day, and propranolol 40 mg/day.
¹⁰Other scheduled oral medications included benztropine 4 mg/day, gemfibrozil 1200 mg/day, olanzapine 2.5 mg/day, and propranolol 60 mg/day.
¹¹Other scheduled oral medications included benztropine 4 mg/day, gemfibrozil 1200 mg/day, olanzapine 2.5 mg/day, and propranolol 120 mg/day.
¹²Other scheduled oral medications included benztropine 4 mg/day, clonidine 0.1 mg/day, gemfibrozil 1200 mg/day, olanzapine 2.5 mg/day, and propranolol 60 mg/day.
¹³Other scheduled oral medications included benztropine 4 mg/day, gemfibrozil 1200 mg/day, olanzapine 2.5 mg/day, and propranolol 60 mg/day.
¹⁴Other scheduled oral medications included benztropine 4 mg/day, clozapine 25 mg/day, gemfibrozil 1200 mg/day, olanzapine 10 mg/day, and propranolol 80 mg/day.
¹⁵Other scheduled oral medications included benztropine 4 mg/day, clozapine 300 mg/day, gemfibrozil 1200 mg/day, olanzapine 10 mg/day, and propranolol 80 mg/day.
¹⁶Other scheduled oral medications included benztropine 4 mg/day, clozapine 600 mg/day, gemfibrozil 1200 mg/day, olanzapine 10 mg/day, and propranolol 80 mg/day.
¹⁷Other scheduled oral medications included benztropine 4 mg/day, clozapine 400 mg/day, gemfibrozil 1200 mg/day, olanzapine 10 mg/day, and propranolol 80 mg/day.
¹⁸Other scheduled oral medications included benztropine 4 mg/day, clozapine 700 mg/day, gemfibrozil 1200 mg/day, olanzapine 10 mg/day, and propranolol 80 mg/day.
¹⁹Other scheduled oral medications included benztropine 4 mg/day, clozapine 800 mg/day, gemfibrozil 1200 mg/day, and propranolol 80 mg/day.
²⁰Other scheduled oral medications included atorvastatin 10 mg/day, benztropine 4 mg/day, clozapine 800 mg/day, and propranolol 80 mg/day.
²¹Other scheduled oral medications included atorvastatin 20 mg/day, benztropine 4 mg/day, clozapine 800 mg/day, and propranolol 80 mg/day.
²²Other scheduled oral medications included atorvastatin 20 mg/day, clozapine 700 mg/day, docusate 250 mg/day, and propranolol 80 mg/day.
²³Other scheduled oral medications included atorvastatin 20 mg/day, benztropine 0.5 mg/day, clozapine 700 mg/day, docusate 250 mg/day, and propranolol 80 mg/day.
²⁴Other scheduled oral medications included atorvastatin 20 mg/day, benztropine 1 mg/day, clozapine 600 mg/day, docusate 250 mg/day, and propranolol 80 mg/day.
²⁵Other scheduled oral medications included atorvastatin 20 mg/day, benztropine 1 mg/day, clozapine 700 mg/day, docusate 250 mg/day, and propranolol 80 mg/day.