Case Reports in Psychiatry / 2015 / Article / Tab 4

Case Report

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

Table 4

VPA C/D ratio in Case 3.

Day1VPAPhenytoin
FormulationDose1 (mg/day)Concentration (μg/mL)C/D ratioC/D ratio × 1000Dose (mg/day)Concentration (μg/mL)

All 137 VPA concentrations (C/D ratio × 1000: mean ± SD = 8 ± 3.5, range = 3–20)
70 therapeutic2 VPA concentrations (C/D ratio × 1000: mean ± SD = 9 ± 3.4, range = 5–18)
13ECDVNa3375460.0141450015
333ECDVNa3375590.0171750018
623ECDVNa 3375430.0131350016
863Concentrate3350220.007 7500
1173ECDVNa3450430.012 1250011
1473ECDVNa3375380.0111150010
1623Concentrate3450 90.003 3500
1743Concentrate3450280.008 850018
1773Concentrate3450310.009 950018
1893ECDVNa3375360.011 11500
2023ECDVNa3750400.0111150010
2083ECDVNa4125400.0101050014
2123ECDVNa 4500680.0151550015
2443ECDVNa4500610.0141450015
2743ECDVNa4500670.0151550015
3073ECDVNa4500460.0101050023
3103ECDVNa4500500.01111 023
3133ECDVNa4500390.009 950010
3163ECDVNa4500810.0181850011
3203ECDVNa4500310.007 750015
3243ECDVNa4500460.010 1050016
3353ECDVNa 5000640.0131350019
3503ECDVNa5000750.0151550024
3983ECDVNa5000520.0101046016
4003ECDVNa 5000850.0171746011
4303ECDVNa5000590.0121246016
4393ECDVNa5000650.0131346018
4703ECDVNa5000540.0111146016
5023ECDVNa5000530.0111146020
5304ECDVNa5000770.0151546017
5594ECDVNa5000500.0101046013
5905ECDVNa5000480.0101046012
6216ECDVNa5000370.007 746010
6356ECDVNa5000390.008 846011
6466ECDVNa5250350.007 746013
6817ECDVNa5250370.007 7460 8
7137ECDVNa5250460.009 9460 7
7347ECDVNa5250400.008 846010
7627ECDVNa6000530.009 9460 9
7707ECDVNa 6000430.007 7460 8
7987ECDVNa6000 230.004 4460 9
8067ECDVNa6000 320.005 546010
8177ECDVNa7500 360.005 5200 9
8317ECDVNa7500 430.006 6460 5
8387ECDVNa7500 470.006 646015
8467ECDVNa7500 240.003 346010
8527ECDVNa7500 350.005 5460 8
8607ECDVNa7500 510.007 7460
8667ECDVNa7500 420.006 6460 3
8887ECDVNa7500 710.009 946020
8907ECDVNa7500 810.011 1146020
9167ECDVNa7500 450.006 6460 7
9197ECDVNa7500 460.006 6460 7
9297ECDVNa8250 430.005 5460
9437ECDVNa9000 430.005 5460
9507ECDVNa9000 500.006 6460
9577ECDVNa9000 750.008 8460
9647ECDVNa9000 370.004 4460
9717ECDVNa9000 280.003 3460
9727ECDVNa9000 440.005 5460 8
9797ECDVNa9000 640.007 7460 6
9857ECDVNa9000 380.004 4460 9
9897ECDVNa9000 500.006 6460 8
9927ECDVNa9000 590.007 7460 9
9997ECDVNa9000 540.006 6460 6
10147ECDVNa9000 350.004 4460 6
10207ECDVNa9000 420.005 5460 5
10297ECDVNa10500 430.004 4460 7
10357ECDVNa105001020.010 10460 6
10397ECDVNa10500 540.005 5460 1
10427ECDVNa10500 770.007 7460 6
10567ECDVNa105001200.011 11460 6
10627ECDVNa10500 390.004 4460 8
10647ECDVNa10500 470.004 4460 7
10707ECDVNa10500 560.005 5460 6
10807ECDVNa10500 510.005 546010
10917ECDVNa10500 540.005 546011
10987ECDVNa10500 630.006 6 46012
11057ECDVNa10500 490.005 546012
11127ECDVNa10500 470.004 4460 8
11197ECDVNa10500 510.005 5460 6
11337ECDVNa10500 910.009 9460 7
11487ECDVNa10500 500.005 546013
11637ECDVNa10500 400.004 4460 9
11687ECDVNa10500 620.006 646010
11757ECDVNa10500 630.006 646013
11827ECDVNa105001100.010 1046011
11847ECDVNa10500 610.006 646010
11897ECDVNa10500 560.005 546010
11967ECDVNa140001330.010 10460 9
12107ECDVNa10500 670.006 646013
12177ECDVNa10500 650.006 646014
12247ECDVNa10500 870.008 846011
12317ECDVNa10500 700.007 746013
12457ECDVNa10500 650.006 646015
12527ECDVNa10500 970.009 9460 9
12597ECDVNa10500 770.007 746013
12667ECDVNa10500 560.005 546012
12737ECDVNa10500 970.009 946014
12807ECDVNa10500 600.006 646016
12878ECDVNa10500 390.004 446019
12948ECDVNa105001030.010 1046015
13018ECDVNa10500 480.005 546019
13078ECDVNa10500 720.007 746013
13168ECDVNa10500 540.005 546013
13228ECDVNa10500 710.007 746013
13298ECDVNa10500 750.007 746013
13368ECDVNa10500 980.009 946012
13448ECDVNa10500 930.009 946011
13508ECDVNa10500 650.006 646015
13578ECDVNa10500 580.006 646023
13648ECDVNa10500 730.007 746018
13718ECDVNa105001060.010 1046024
13738ECDVNa105001060.010 1046020
13788ECDVNa10500 890.008 846015
13868ECDVNa10500 970.009 946017
13928ECDVNa10500 720.007 746021
13938ECDVNa10500 870.008 846023
13948ECDVNa105001220.012 1223022
13958ECDVNa3500 370.011 11 020
13998ECDVNa105001300.012 12400 8
14068ECDVNa10500 940.009 940010
14138ECDVNa105001260.012 1240012
14208ECDVNa105001080.010 1040012
14278ECDVNa6000 590.010 1040021
14358ECDVNa90001100.01212400 5
14408ECDVNa9000 860.01010400 8
14448ECDVNa9000 820.009 940010
14488ECDVNa90001470.0161640010
14547ECDVNa7000 930.0131340014
14579ECDVNa70001380.0202040011
146110ECDVNa7000 720.0101040013
147011ECDVNa70001010.0141440013
1478ECDVNa70001130.01616400 7
1483ECDVNa7000 970.01414400 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.

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