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

Table 4

VPA C/D ratio in Case 3.

Day^1	VPA					Phenytoin
	Formulation	Dose^1 (mg/day)	Concentration (μg/mL)	C/D ratio	C/D ratio × 1000	Dose (mg/day)	Concentration (μg/mL)
All 137 VPA concentrations (C/D ratio × 1000: mean ± SD = 8 ± 3.5, range = 3–20)
70 therapeutic^2 VPA concentrations (C/D ratio × 1000: mean ± SD = 9 ± 3.4, range = 5–18)
1^3	ECDVNa	3375	46	0.014	14	500	15
33^3	ECDVNa	3375	59	0.017	17	500	18
62^3	ECDVNa	3375	43	0.013	13	500	16
86^3	Concentrate	3350	22	0.007	7	500
117^3	ECDVNa	3450	43	0.012	12	500	11
147^3	ECDVNa	3375	38	0.011	11	500	10
162^3	Concentrate	3450	9	0.003	3	500
174^3	Concentrate	3450	28	0.008	8	500	18
177^3	Concentrate	3450	31	0.009	9	500	18
189^3	ECDVNa	3375	36	0.011	11	500
202^3	ECDVNa	3750	40	0.011	11	500	10
208^3	ECDVNa	4125	40	0.010	10	500	14
212^3	ECDVNa	4500	68	0.015	15	500	15
244^3	ECDVNa	4500	61	0.014	14	500	15
274^3	ECDVNa	4500	67	0.015	15	500	15
307^3	ECDVNa	4500	46	0.010	10	500	23
310^3	ECDVNa	4500	50	0.011	11	0	23
313^3	ECDVNa	4500	39	0.009	9	500	10
316^3	ECDVNa	4500	81	0.018	18	500	11
320^3	ECDVNa	4500	31	0.007	7	500	15
324^3	ECDVNa	4500	46	0.010	10	500	16
335^3	ECDVNa	5000	64	0.013	13	500	19
350^3	ECDVNa	5000	75	0.015	15	500	24
398^3	ECDVNa	5000	52	0.010	10	460	16
400^3	ECDVNa	5000	85	0.017	17	460	11
430^3	ECDVNa	5000	59	0.012	12	460	16
439^3	ECDVNa	5000	65	0.013	13	460	18
470^3	ECDVNa	5000	54	0.011	11	460	16
502^3	ECDVNa	5000	53	0.011	11	460	20
530^4	ECDVNa	5000	77	0.015	15	460	17
559^4	ECDVNa	5000	50	0.010	10	460	13
590^5	ECDVNa	5000	48	0.010	10	460	12
621^6	ECDVNa	5000	37	0.007	7	460	10
635^6	ECDVNa	5000	39	0.008	8	460	11
646^6	ECDVNa	5250	35	0.007	7	460	13
681^7	ECDVNa	5250	37	0.007	7	460	8
713^7	ECDVNa	5250	46	0.009	9	460	7
734^7	ECDVNa	5250	40	0.008	8	460	10
762^7	ECDVNa	6000	53	0.009	9	460	9
770^7	ECDVNa	6000	43	0.007	7	460	8
798^7	ECDVNa	6000	23	0.004	4	460	9
806^7	ECDVNa	6000	32	0.005	5	460	10
817^7	ECDVNa	7500	36	0.005	5	200	9
831^7	ECDVNa	7500	43	0.006	6	460	5
838^7	ECDVNa	7500	47	0.006	6	460	15
846^7	ECDVNa	7500	24	0.003	3	460	10
852^7	ECDVNa	7500	35	0.005	5	460	8
860^7	ECDVNa	7500	51	0.007	7	460
866^7	ECDVNa	7500	42	0.006	6	460	3
888^7	ECDVNa	7500	71	0.009	9	460	20
890^7	ECDVNa	7500	81	0.011	11	460	20
916^7	ECDVNa	7500	45	0.006	6	460	7
919^7	ECDVNa	7500	46	0.006	6	460	7
929^7	ECDVNa	8250	43	0.005	5	460
943^7	ECDVNa	9000	43	0.005	5	460
950^7	ECDVNa	9000	50	0.006	6	460
957^7	ECDVNa	9000	75	0.008	8	460
964^7	ECDVNa	9000	37	0.004	4	460
971^7	ECDVNa	9000	28	0.003	3	460
972^7	ECDVNa	9000	44	0.005	5	460	8
979^7	ECDVNa	9000	64	0.007	7	460	6
985^7	ECDVNa	9000	38	0.004	4	460	9
989^7	ECDVNa	9000	50	0.006	6	460	8
992^7	ECDVNa	9000	59	0.007	7	460	9
999^7	ECDVNa	9000	54	0.006	6	460	6
1014^7	ECDVNa	9000	35	0.004	4	460	6
1020^7	ECDVNa	9000	42	0.005	5	460	5
1029^7	ECDVNa	10500	43	0.004	4	460	7
1035^7	ECDVNa	10500	102	0.010	10	460	6
1039^7	ECDVNa	10500	54	0.005	5	460	1
1042^7	ECDVNa	10500	77	0.007	7	460	6
1056^7	ECDVNa	10500	120	0.011	11	460	6
1062^7	ECDVNa	10500	39	0.004	4	460	8
1064^7	ECDVNa	10500	47	0.004	4	460	7
1070^7	ECDVNa	10500	56	0.005	5	460	6
1080^7	ECDVNa	10500	51	0.005	5	460	10
1091^7	ECDVNa	10500	54	0.005	5	460	11
1098^7	ECDVNa	10500	63	0.006	6	460	12
1105^7	ECDVNa	10500	49	0.005	5	460	12
1112^7	ECDVNa	10500	47	0.004	4	460	8
1119^7	ECDVNa	10500	51	0.005	5	460	6
1133^7	ECDVNa	10500	91	0.009	9	460	7
1148^7	ECDVNa	10500	50	0.005	5	460	13
1163^7	ECDVNa	10500	40	0.004	4	460	9
1168^7	ECDVNa	10500	62	0.006	6	460	10
1175^7	ECDVNa	10500	63	0.006	6	460	13
1182^7	ECDVNa	10500	110	0.010	10	460	11
1184^7	ECDVNa	10500	61	0.006	6	460	10
1189^7	ECDVNa	10500	56	0.005	5	460	10
1196^7	ECDVNa	14000	133	0.010	10	460	9
1210^7	ECDVNa	10500	67	0.006	6	460	13
1217^7	ECDVNa	10500	65	0.006	6	460	14
1224^7	ECDVNa	10500	87	0.008	8	460	11
1231^7	ECDVNa	10500	70	0.007	7	460	13
1245^7	ECDVNa	10500	65	0.006	6	460	15
1252^7	ECDVNa	10500	97	0.009	9	460	9
1259^7	ECDVNa	10500	77	0.007	7	460	13
1266^7	ECDVNa	10500	56	0.005	5	460	12
1273^7	ECDVNa	10500	97	0.009	9	460	14
1280^7	ECDVNa	10500	60	0.006	6	460	16
1287^8	ECDVNa	10500	39	0.004	4	460	19
1294^8	ECDVNa	10500	103	0.010	10	460	15
1301^8	ECDVNa	10500	48	0.005	5	460	19
1307^8	ECDVNa	10500	72	0.007	7	460	13
1316^8	ECDVNa	10500	54	0.005	5	460	13
1322^8	ECDVNa	10500	71	0.007	7	460	13
1329^8	ECDVNa	10500	75	0.007	7	460	13
1336^8	ECDVNa	10500	98	0.009	9	460	12
1344^8	ECDVNa	10500	93	0.009	9	460	11
1350^8	ECDVNa	10500	65	0.006	6	460	15
1357^8	ECDVNa	10500	58	0.006	6	460	23
1364^8	ECDVNa	10500	73	0.007	7	460	18
1371^8	ECDVNa	10500	106	0.010	10	460	24
1373^8	ECDVNa	10500	106	0.010	10	460	20
1378^8	ECDVNa	10500	89	0.008	8	460	15
1386^8	ECDVNa	10500	97	0.009	9	460	17
1392^8	ECDVNa	10500	72	0.007	7	460	21
1393^8	ECDVNa	10500	87	0.008	8	460	23
1394^8	ECDVNa	10500	122	0.012	12	230	22
1395^8	ECDVNa	3500	37	0.011	11	0	20
1399^8	ECDVNa	10500	130	0.012	12	400	8
1406^8	ECDVNa	10500	94	0.009	9	400	10
1413^8	ECDVNa	10500	126	0.012	12	400	12
1420^8	ECDVNa	10500	108	0.010	10	400	12
1427^8	ECDVNa	6000	59	0.010	10	400	21
1435^8	ECDVNa	9000	110	0.012	12	400	5
1440^8	ECDVNa	9000	86	0.010	10	400	8
1444^8	ECDVNa	9000	82	0.009	9	400	10
1448^8	ECDVNa	9000	147	0.016	16	400	10
1454^7	ECDVNa	7000	93	0.013	13	400	14
1457^9	ECDVNa	7000	138	0.020	20	400	11
1461^10	ECDVNa	7000	72	0.010	10	400	13
1470^11	ECDVNa	7000	101	0.014	14	400	13
1478	ECDVNa	7000	113	0.016	16	400	7
1483	ECDVNa	7000	97	0.014	14	400	6

C/D: concentration-to-dose; ECDVNa: enterocoated divalproex sodium; VPA: valproic acid.
¹After day 1420, VPA dose was guided more by physical comfort than VPA concentrations; therefore, these latter days were eliminated to calculate the Pearson correlation between day of admission and VPA dose, which was (); VPA dose remained very high 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. When all values (including those after day 1420) were used to calculate correlations, the values were, not surprisingly, slightly reduced both for the total correlation of () and the partial correlation of ().
²50–100 μg/mL concentrations are considered therapeutic concentrations. As this patient has too many nontherapeutic concentrations, it may be better to compare with other patients using only the VPA therapeutic concentrations.
³Other scheduled oral medications included benztropine 4 mg/day, mesoridazine 200 mg/day, lorazepam 6 mg/day, and risperidone 12 mg/day.
⁴Other scheduled oral medications included benztropine 4 mg/day, lorazepam 6 mg/day, and risperidone 12 mg/day.
⁵Other scheduled oral medications included benztropine 4 mg/day, lorazepam 6 mg/day, and risperidone 4 mg/day.
⁶Other scheduled oral medications included benztropine 4 mg/day and lorazepam 6 mg/day.
⁷Other scheduled oral medications included lorazepam 6 mg/day.
⁸Other scheduled oral medications included lorazepam 6 mg/day and trazodone 150 mg/day.
⁹Other scheduled oral medications included lorazepam 4 mg/day.
¹⁰Other scheduled oral medications included lorazepam 3 mg/day.
¹¹Other scheduled oral medications included lorazepam 1 mg/day.