Valproic acid autoinduction: a case-based review
Tóm tắt
Although valproic acid (VPA) induces the metabolism of multiple other drugs, the clinical reports of VPA autoinduction are rare. A comprehensive literature search yielded only one published case series, which provided the rationale to conduct a review of the published cases along with a new case of VPA autoinduction. Although there may be myriad of reasons for lack of published cases of VPA autoinduction, potential underreporting may be one of the core reasons. Lack of understanding into the highly complex metabolism of VPA may also make it difficult to recognize and report VPA autoinduction. However, it is important to mention that in addition to autoinduction increased elimination of VPA may be mediated by several pharmacokinetic (PK) factors, such as drug interactions, genetic polymorphisms of metabolic enzymes, and protein displacement reactions. As VPA is metabolized by multiple metabolic pathways, the risk for drug interactions is relatively high. There is also a growing evidence for high genetic inducibility of some enzymes involved in VPA metabolism. Protein displacement reactions with VPA increase the biologically active and readily metabolizable free fraction and pose a diagnostic challenge as they are usually not requested by most clinicians. Thus, monitoring of free fraction with total VPA levels may prevent clinically serious outcomes and optimize VPA treatment in clinically challenging patients. This case-based review compares the clinical data from three published cases and a new case of VPA autoinduction to enhance clinicians' awareness of this relatively rare but clinically relevant phenomenon along with a discussion of potential underlying mechanisms.
Tài liệu tham khảo
Bergemann N, Kress KR, Abu-Tair F, Frick A, Kopitz J. Valproate lowers plasma concentration of olanzapine. J Clin Psychopharmacol. 2006;26(4):432–4.
Cerveny L, Svecova L, Anzenbacherova E, Vrzal R, Staud F, Dvorak Z, et al. Valproic acid induces CYP3A4 and MDR1 gene expression by activation of constitutive androstane receptor and pregnane X receptor pathways. Drug Metab Dispos. 2007;35(7):1032–41.
Citrome L, Josiassen R, Bark N, Salazar DE, Mallikaarjun S. Pharmacokinetics of aripiprazole and concomitant lithium and valproate. J Clin Pharmacol. 2005;45(1):89–93.
de Leon J. The effects of antiepileptic inducers in neuropsychopharmacology, a neglected issue. Part II: pharmacological issues and further understanding. Rev Psiquiatr Salud Ment. 2015;8(3):167–88.
de Leon J. The effects of antiepileptic inducers in neuropsychopharmacology, a neglected issue. Part I: a summary of the current state for clinicians. Rev Psiquiatr Salud Ment. 2015b;8(2):97–115.
de Jong FA, Scott-Horton TJ, Kroetz DL, McLeod HL, Friberg LE, Mathijssen RH, et al. Irinotecan-induced diarrhea: functional significance of the polymorphic ABCC2 transporter protein. Clin Pharmacol Ther. 2007;81(1):42–9.
de Maat MM, van Leeuwen HJ, Edelbroek PM. High unbound fraction of valproic acid in a hypoalbuminemic critically ill patient on renal replacement therapy. Ann Pharmacother. 2011;45(3):e18.
Diaz FJ, Eap CB, Ansermot N, Crettol S, Spina E, de Leon J. Can valproic acid be an inducer of clozapine metabolism? Pharmacopsychiatry. 2014;47(3):89–96.
Ding J, Wang Y, Lin W, Wang C, Zhao L, Li X, et al. A population pharmacokinetic model of valproic acid in pediatric patients with epilepsy: a non-linear pharmacokinetic model based on protein-binding saturation. Clin Pharmacokinet. 2015;54(3):305–17.
Dutta S, Faught E, Limdi NA. Valproate protein binding following rapid intravenous administration of high doses of valproic acid in patients with epilepsy. J Clin Pharm Ther. 2007;32(4):365–71.
Finley P, Warner D. Potential impact of valproic acid therapy on clozapine disposition. Biol Psychiat. 1994;36(7):487–8.
Fisher JE, Nau H, Loscher W. Alterations in the renal excretion of valproate and its metabolites after chronic treatment. Epilepsia. 1991;32(1):146–50.
Franco V, Perucca E. CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects. Expert Opin Drug Metab Toxicol. 2015;11(8):1269–79.
Ghodke-Puranik Y, Thorn CF, Lamba JK, Leeder JS, Song W, Birnbaum AK, et al. Valproic acid pathway: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. 2013;23(4):236–41.
Guo Y, Hu C, He X, Qiu F, Zhao L. Effects of UGT1A6, UGT2B7, and CYP2C9 genotypes on plasma concentrations of valproic acid in Chinese children with epilepsy. Drug Metab Pharmacokinet. 2012;27(5):536–42.
Haslemo T, Olsen K, Lunde H, Molden E. Valproic acid significantly lowers serum concentrations of olanzapine-an interaction effect comparable with smoking. Ther Drug Monit. 2012;34(5):512–7.
Hermida J, Tutor JC. A theoretical method for normalizing total serum valproic acid concentration in hypoalbuminemic patients. J Pharmacol Sci. 2005;97(4):489–93.
Hooper WD, Franklin ME, Glue P, Banfield CR, Radwanski E, McLaughlin DB, et al. Effect of felbamate on valproic acid disposition in healthy volunteers: inhibition of beta-oxidation. Epilepsia. 1996;37(1):91–7.
Hung CC, Ho JL, Chang WL, Tai JJ, Hsieh TJ, Hsieh YW, et al. Association of genetic variants in six candidate genes with valproic acid therapy optimization. Pharmacogenomics. 2011;12(8):1107–17.
Jackson J, McCollum B, Ognibene J, Diaz FJ, de Leon J. Three patients needing high doses of valproic acid to get therapeutic concentrations. Case Rep Psychiatry. 2015;2015:542862.
Jiang D, Bai X, Zhang Q, Lu W, Wang Y, Li L, et al. Effects of CYP2C19 and CYP2C9 genotypes on pharmacokinetic variability of valproic acid in Chinese epileptic patients: nonlinear mixed-effect modeling. Eur J Clin Pharmacol. 2009;65(12):1187–93.
Kallen B. Valproic acid is known to cause hypospadias in man but does not reduce anogenital distance or causes hypospadias in rats. Basic Clin Pharmacol Toxicol. 2004;94(1):51–4.
Kim SC, Kim MG. A meta-analysis of the influence of UGT1A6 genetic polymorphisms on valproic acid pharmacokinetics. Int J Clin Pharmacol Ther. 2019;57:144–51.
Kodama Y, Kodama H, Kuranari M, Tsutsumi K, Ono S, Yukawa E, et al. Gender- or age-related binding characteristics of valproic acid to serum proteins in adult patients with epilepsy. Eur J Pharm Biopharm. 2001;52(1):57–63.
Lai ML, Huang JD. Dual effect of valproic acid on the pharmacokinetics of phenytoin. Biopharm Drug Dispos. 1993;14(4):365–70.
Lampen A, Siehler S, Ellerbeck U, Gottlicher M, Nau H. New molecular bioassays for the estimation of the teratogenic potency of valproic acid derivatives in vitro: activation of the peroxisomal proliferator-activated receptor (PPARdelta). Toxicol Appl Pharmacol. 1999;160(3):238–49.
Lana F, Marti-Bonany J, Fuster J, de Leon J. Reduction in serum concentration of valproic acid secondary to the intake of ibuprofen as an example of valproic acid auto-induction metabolism. Actas Esp Psiquiatr. 2016a;44(4):136–44.
Lana F, Marti-Bonany J, de Leon J. Ibuprofen may increase pharmacological action of valproate by displacing it from plasma proteins: a case report. Am J Psychiatry. 2016b;173(9):941–2.
Li Q, Lugt CB, Looareesuwan S, Krudsood S, Wilairatana P, Vannaphan S, et al. Pharmacokinetic investigation on the therapeutic potential of artemotil (beta-arteether) in Thai patients with severe Plasmodium falciparum malaria. Am J Trop Med Hyg. 2004;71(6):723–31.
Longo LP, Salzman C. Valproic acid effects on serum concentrations of clozapine and norclozapine. Am J Psychiatry. 1995;152(4):650.
Luci S, Geissler S, Konig B, Koch A, Stangl GI, Hirche F, et al. PPARalpha agonists up-regulate organic cation transporters in rat liver cells. Biochem Biophys Res Commun. 2006;350(3):704–8.
Lutz JD, Kirby BJ, Wang L, Song Q, Ling J, Massetto B, et al. Cytochrome P450 3A Induction Predicts P-glycoprotein Induction; Part 2: prediction of decreased substrate exposure after rifabutin or carbamazepine. Clin Pharmacol Ther. 2018;104(6):1191–8.
McLaughlin DB, Eadie MJ, Parker-Scott SL, Addison RS, Henderson RD, Hooper WD, et al. Valproate metabolism during valproate-associated hepatotoxicity in a surviving adult patient. Epilepsy Res. 2000;41(3):259–68.
Methaneethorn J. A systematic review of population pharmacokinetics of valproic acid. Br J Clin Pharmacol. 2018;84(5):816–34.
Morris RG, Black AB, Lam E, Westley IS. Clinical study of lamotrigine and valproic acid in patients with epilepsy: using a drug interaction to advantage? Ther Drug Monit. 2000;22:656–60.
Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs. Lancet Neurol. 2003;2(8):473–81.
Patsalos PN, Berry DJ, Bourgeois BF, Cloyd JC, Glauser TA, Johannessen SI, et al. Antiepileptic drugs–best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia. 2008;49(7):1239–76.
Perucca E, Hebdige S, Frigo GM, Gatti G, Lecchini S, Crema A. Interaction between phenytoin and valproic acid: plasma protein binding and metabolic effects. Clin Pharmacol Ther. 1980;28(6):779–89.
Perucca E, Berlowitz D, Birnbaum A, Cloyd JC, Garrard J, Hanlon JT, et al. Pharmacological and clinical aspects of antiepileptic drug use in the elderly. Epilepsy Res. 2006;68(Suppl 1):S49-63.
Peterson GM, Naunton M. Valproate: a simple chemical with so much to offer. J Clin Pharm Ther. 2005;30(5):417–21.
Sun Y, Yu J, Yuan Q, Wu X, Wu X, Hu J. Early post-traumatic seizures are associated with valproic acid plasma concentrations and UGT1A6/CYP2C9 genetic polymorphisms in patients with severe traumatic brain injury. Scand J Trauma Resusc Emerg Med. 2017;25:85.
Tanner JA, Tyndale RF. Variation in CYP2A6 activity and personalized medicine. J Pers Med. 2017;7:18.
VandenBerg A, Broadway J, Lalich C, Kennedy R, Williams K. Valproate serum concentrations in patients with hypoalbuminemia and medical complications. Ment Health Clin. 2017;7:13–5.
Wang S, Zhou N. Removal of carbamazepine from aqueous solution using sono-activated persulfate process. Ultrason Sonochem. 2016;29:156–62.
Wang P, Lin XQ, Cai WK, Xu GL, Zhou MD, Yang M, He GH. Effect of UGT2B7 genotypes on plasma concentration of valproic acid: a meta-analysis. Eur J Clin Pharmacol. 2018;74:433–42.
Wen X, Wang JS, Kivisto KT, Neuvonen PJ, Backman JT. In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9). Br J Clin Pharmacol. 2001;52(5):547–53.
Werling U, Siehler S, Litfin M, Nau H, Gottlicher M. Induction of differentiation in F9 cells and activation of peroxisome proliferator-activated receptor delta by valproic acid and its teratogenic derivatives. Mol Pharmacol. 2001;59(5):1269–76.
Zaccara G, Giovannelli F, Bell GS, Sander JW. Network meta-analyses of antiepileptic drug efficacy and tolerability in drug-resistant focal epilepsies: a clinical perspective. Eur J Clin Pharmacol. 2014;70(6):647–54.