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Free and Total Serum Valproate Concentrations: Their Relationship to Seizure Control, Liver Enzymes and Plasma Ammonia in Children

Published online by Cambridge University Press:  18 September 2015

Kevin Farrell ,
Frank S. Abbott ,
James M. Orr ,
Derek A. Applegarth ,
James E. Jan  and
Peter K. Wong
Kevin Farrell*
Affiliation:
Department of Paediatrics and Faculty of Pharmaceutical Sciences, University of British Columbia
Frank S. Abbott
Affiliation:
Department of Paediatrics and Faculty of Pharmaceutical Sciences, University of British Columbia
James M. Orr
Affiliation:
Department of Paediatrics and Faculty of Pharmaceutical Sciences, University of British Columbia
Derek A. Applegarth
Affiliation:
Department of Paediatrics and Faculty of Pharmaceutical Sciences, University of British Columbia
James E. Jan
Affiliation:
Department of Paediatrics and Faculty of Pharmaceutical Sciences, University of British Columbia
Peter K. Wong
Affiliation:
Department of Paediatrics and Faculty of Pharmaceutical Sciences, University of British Columbia
*
Division of Neurology, British Columbia's Children's Hospital, 4480 Oak Street, Vancouver, B.C, Canada V6H 3V4
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Abstract:

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The relationships between total and free serum valproate (VPA) concentrations and seizure control, serum liver enzyme activity and plasma ammonia concentration were studied in 61 epileptic children. Enzymeimmunoassay (EMIT)R methods gave higher values of total VPA concentration than gas-liquid chromatography (GLC) methods. In over 80% of children with complete seizure control the ranges of total VPA concentration were 140-420 umol/L with GLC methods and 210-560 umol/L with EMIT methods. The range of free VPA concentrations in 78% of children with complete seizure control was 8.8-26.4 umol/L. Increased liver enzyme activity was observed in 6 of the 61 children and raised plasma ammonia concentration in 11 of 50 children. Plasma ammonia concentration was related to total serum VPA but was not related to free serum VPA. Increased serum liver enzyme activity was related to VPA dose per kg but not to free or total serum VPA concentration. Thus free VPA concentrations do not appear to be more useful than total VPA concentrations in predicting seizure control and do not correlate with liver enzyme activity or plasma ammonia concentration.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 13 , Issue 3 , August 1986 , pp. 252 - 255
Copyright
Copyright © Canadian Neurological Sciences Federation 1986

References

1.Meinardi, H, Hanke, NFJ, Beveren, JV.Sodiumdi-N-prophylacetate: estimation of effective serum levels. Pharmacol Week 1974; 109: 45–47.Google Scholar
2.Wilder, BJ, Karas, BJ.Valproate: Relation of plasma concentration to seizure control (Chap 48) In: Woodbury, BM, Penry, JK, Pippenger, CE, eds. Antiepileptic drugs. New York, NY: Raven Press, 1982: 591–600.Google ScholarPubMed
3.Klotz, U, Schweizer, C.Valproic acid in childhood epilepsy: anticonvulsive efficacy in relation to its plasma levels. Int J Clin Pharm 1980; 18: 461–465.Google ScholarPubMed
4.Rowan, AJ, Binnie, CD, De Beer-Pawlikowski, NKB, Goedhart, DM, Gutter, T, Van der Geest, P, Meinardi, H, Meijer, JWA.Sodium valproate: Serial monitoring of EEG and serum levels. Neurology 1979; 29: 1450–1459.CrossRefGoogle ScholarPubMed
5.Herranz, JL, Arteaga, R, Armijo, JA.Side effects of sodium valproate in monotherapy controlled by plasma levels: A study in 88 pediatric patients, Epilepsia 1982; 23: 203–214.CrossRefGoogle Scholar
6.Covanis, A, Gupta, AK, Jeavons, PM.Sodium valproate: Monotherapy and polytherapy. Epilepsia 1982; 23: 693–720.CrossRefGoogle ScholarPubMed
7.Vining, EPG, Botsford, E, et al. Valproate sodium in refractory seizures. Am J Dis Child 1979; 13: 274–276.CrossRefGoogle Scholar
8.Murphy, JV, Marquardt, K.Asymptomatic hyperammonemia in patients receiving valproic acid. Arch Neurol 1982; 39: 591–592.CrossRefGoogle ScholarPubMed
9.Williams, CA, Tiefenbach, S, Mcreynold, JW.Valproic acid-induced hyperammonemia in mentally retarded adults. Neurology (Ny) 1984; 34: 550–553.CrossRefGoogle ScholarPubMed
10.Wyllie, E, Wyllie, R, Rothner, AD.Valproate-induced hyperammonemia in asymptomatic children. Ann of Neurol 1982; 12: 208.Google Scholar
11.Ohtani, Y, Endo, F, Matsuda, I.Carnitine deficiency and hyperammonemia associated with valproic acid therapy. J of Pediatr 1982; 101: 782–785.CrossRefGoogle ScholarPubMed
12.Haidukewych, D, John, G, Zielinski, JJ, Rodin, EA.Chronic valproic acid therapy and incidence of increases in venous plasma ammonia. Therapeutic Drug Monitoring 1985; 7: 290–294.CrossRefGoogle ScholarPubMed
13.Levy, RH.Monitoring of free valproic acid levels. Ther Drug Monitoring 1980; 2: 199–201.CrossRefGoogle ScholarPubMed
14.Orr, JM, Abbott, FS, Farrell, K, Ferguson, S, Sheppard, I, Godolphin, W.Interaction between valproic acid and Aspirin in epileptic children: Serum protein binding and metabolic effects. Clin Pharmacol Ther. 1982; 31: 642–649.CrossRefGoogle ScholarPubMed
15.Abbott, FS, Burton, R, Orr, J, Wladichuk, D, Ferguson, S, Sun, T.Valproic acid analysis in saliva and serum using selected ion monitoring (Electron ionization) of the tertbutyl-dimethylsilyl derivatives. J of Chromatography 1982; 227: 433–444.CrossRefGoogle Scholar
16.Verity, CM, Farrell, K, Applegarth, DA, Kirby, LT.The influence of anticonvulsants on fasting plasma ammonia and amino acids. Clin Biochem 1983; 344–345.CrossRefGoogle Scholar
17.Henriksen, O, Johannessen, SI.Clinical and pharmacokinetic observations on sodium valproate - A 5-year follow-up study in 100 children with epilepsy. Acta Neurol Scandinav. 1982; 65:504–523.CrossRefGoogle ScholarPubMed
18.Trimble, MR, Thompson, PJ.Anticonvulsant Drugs, Cognitive Function, and Behaviour. Epilepsia. 1983:24(Suppl. 1); S55–S63.CrossRefGoogle Scholar
19.Vajda, FJE and Aicardi, J.Reassessment of the concept of a therapeutic range of anticonvulsant plasma levels. Dev Med and Child Neurol 1983; 25: 660–671.CrossRefGoogle ScholarPubMed
20.Kutt, H.Phenytoin: relation of plasma concentration to seizure control. In: Woodbury, DM, Penry, JK, Pippenger, CE, eds. Antiepileptic drugs. New York: Raven Press, 1982: 241–6.Google Scholar
21.Schmidt, D, Haenel, F.Therapeutic plasma levels of phenytoin, phénobarbital, and carbamazepine: Individual variation in relation to seizure frequency and type. Neurol 1984; 34: 1252–5.CrossRefGoogle ScholarPubMed
22.Kumps, AH, Jumps-Grandjean, B, Mardens, Y.Enzyme Immunoassay and gas liquid chromatography compared for determination of valproic acid in serum. Clin Chem 1981; 27: 1788–1789.CrossRefGoogle ScholarPubMed
23.Monaco, F, Piredda, S.Carbamazepine-10,11-Epoxide determined by EMIT carbamazepine reagent. Epilepsia 1980; 21: 475–477.CrossRefGoogle ScholarPubMed
24.Levy, RH, Moreland, TA.Rationale for monitoring free drug levels. Clin Pharmacokin 1984; 9 (Suppl. 1): 109.CrossRefGoogle ScholarPubMed
25.Lockard, JS, Levy, RH, Congdon, WC, Ducharme, LL, Rhodes, PH.Valproate nonreversibility: Dosing procedures critical?In: Levy, RHet al eds. Metabolism of anti-epileptic drugs. New York, NY: Raven Press, 1984: 153–163.Google Scholar
26.Coulter, DL, Allen, RJ.Secondary hyperammonemia: A possible mechanism for valproate encephalopathy. The Lancet 1980: 1310–1311.CrossRefGoogle ScholarPubMed
27.Hokanson, JT, O’Brien, WE, Idemotor, J, Schafer, IA.Carrier detection in ornithine transcarbamylase deficiency. J Pediatr 1978;93: 75–78.CrossRefGoogle ScholarPubMed
28.Green, SH.Sodium valproate and routine liver function test. Arch Dis Child 1984; 59: 812–814.CrossRefGoogle Scholar
29.Kochen, W, Schneider, A, Ritz, A.Abnormal metabolism of valproic acid in fatal hepatic failure. Eur J Pediatr 1983; 141: 30–35.CrossRefGoogle ScholarPubMed