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Pharmacopsychiatry 2013; 46(03): 83-87
DOI: 10.1055/s-0032-1323783
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Serum Levels of Sodium Valproate in Patients Suffering from Bipolar Disorders: Comparing Acute and Maintenance Phases of Mania

G. Kamalinia
1   Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
,
S. Brand
2   Psychiatric Hospital of the University of Basel, Center for Affective, Sleep, Stress Disorders, Basel, Switzerland
,
P. Ghaeli
1   Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
3   Roozbeh Psychiatric Hospital and Psychiatry and Psychology Research Center, Tehran, Iran
,
N. Abedi
3   Roozbeh Psychiatric Hospital and Psychiatry and Psychology Research Center, Tehran, Iran
,
H. Bajoghli
3   Roozbeh Psychiatric Hospital and Psychiatry and Psychology Research Center, Tehran, Iran
,
V. Sharifi
3   Roozbeh Psychiatric Hospital and Psychiatry and Psychology Research Center, Tehran, Iran
,
A. Zahiroddin
4   Behavioral Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
M. Amini
1   Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
,
M. R. Rouini
1   Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
,
E. Holsboer-Trachsler
2   Psychiatric Hospital of the University of Basel, Center for Affective, Sleep, Stress Disorders, Basel, Switzerland
,
A. H. Mohammadpoor
5   Pharmaceutical Research Center & School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
› Author Affiliations
Further Information

Publication History

received 24 May 2012
revised 07 August 2012

accepted 21 August 2012

Publication Date:
23 October 2012 (online)

Also available at
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Abstract

Objectives:

Bipolar disorders (BD) are characterized by episodes of mania and depression. There is evidence that states of psychiatric disorders impact on neurotransmitters, endocrine system and membrane transport and, therefore, it is possible that specific phases of BD differentially influence the pharmacokinetics of some drugs. The aim of the present study was to investigate the drug-disease interaction between sodium valproate, one of the major drugs used in the treatment of bipolar disorder, and acute versus maintenance states of manic episodes.

Method:

37 patients (mean age±SD=37.54±11.27 years; 23 males, 14 females) suffering from bipolar disorder completed the study. Blood samples were taken during both acute and maintenance states.

Results:

Neither the trough concentration (p=0.567) nor the internal clearances (p=0.729) of sodium valproate in the acute phase of mania differed statistically or descriptively from those in the maintenance phase. Marginally significant phase by gender interactions were observed.

Conclusion:

No significant effect of the acute phase of mania was observed in bipolar patients and no relationship could be found between drug pharmacokinetics and disease phase. This may be explained by specific pharmacokinetic features of the drug such as low extraction ratio values. However, phase by gender interactions indicate possible gender-related issues.

Key words

sodium valproate - bipolar disorder - drug-disease interaction - pharmacokinetics
 

  • References

  • 1 American Psychiatric Association . Diagnostic and statistical manual of mental disorders. 4 ed. Washington, DC: Authors; 2000
    Search in Google Scholar
  • 2 Merikangas KR, Jin R, He JP et al. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry 2011; 68: 241-251
    CrossrefPubMedSearch in Google Scholar
  • 3 Fiedorowicz JG, Palagummi NM, Forman-Hoffman VL et al. Elevated prevalence of obesity, metabolic syndrome, and cardiovascular risk factors in bipolar disorder. Ann Clin Psychiatry 2008; 20: 131-137
    CrossrefPubMedSearch in Google Scholar
  • 4 Allen MH, Hirschfeld RM, Wozniak PJ et al. Linear relationship of valproate serum concentration to response and optimal serum levels for acute mania. Am J Psychiatry 2006; 163: 272-275
    CrossrefPubMedSearch in Google Scholar
  • 5 Lacy CF, Armstrong LL, Goldman MP et al. Drug Information Handbook 2006-2007. Washington, DC: The American Pharmaceutical Association; 2006
    Search in Google Scholar
  • 6 Johannessen CU, Johannessen SI. Valproate: past, present, and future. CNS Drug Rev 2003; 9: 199-216
    PubMedSearch in Google Scholar
  • 7 Lagace DC, O’Brien T, Gurvich N, Nachtigal MW, Klein PS. Valproic acid: how it works. Or not. Clin Neuroscie Res 2004; 4: 215-225
    PubMedSearch in Google Scholar
  • 8 Akhondzadeh S, Mohajari H, Reza Mohammadi M et al. Ritanserin as an adjunct to lithium and haloperidol for the treatment of medication-naive patients with acute mania: a double blind and placebo controlled trial. BMC Psychiatry 2003; 3: 7
    CrossrefPubMedSearch in Google Scholar
  • 9 Daneshtalab N, Lewanczuk RZ, Russell AS et al. Drug-disease interactions: losartan effect is not downregulated by rheumatoid arthritis. J Clin Pharmacol 2006; 46: 1344-1355
    CrossrefPubMedSearch in Google Scholar
  • 10 Kulmatycki KM, Jamali F. Drug disease interactions: role of inflammatory mediators in depression and variability in antidepressant drug response. J Pharm Pharm Sci 2006; 9: 292-306
    PubMedSearch in Google Scholar
  • 11 Sanaee F, Clements JD, Waugh AW et al. Drug-disease interaction: Crohn's disease elevates verapamil plasma concentrations but reduces response to the drug proportional to disease activity. Br J Clin Pharmacol 2011; 72: 787-797
    CrossrefPubMedSearch in Google Scholar
  • 12 DiPiro JT, Talbert RL, Yee GC et al. Pharmacotherapy: a pathophysiological approach. 4 ed. Stamford (CT): Appleton and Lange; 1999
    Search in Google Scholar
  • 13 Mohammadpour AH, Ghaeli P, Sadray S et al. Comparison of carbamazepine clearance between epileptic patients and patients with acute mania. Daru 2004; 12: 141-145
    PubMedSearch in Google Scholar
  • 14 Kamalinia G, Rouini MR, Ghaeli P et al. N-(1-Naphthyl)ethylenediamine, a new UV labeling reagent used for LC determination of valproic acid in human plasma. Chromatographia 2009; 70: 569-573
    CrossrefPubMedSearch in Google Scholar
  • 15 Berwaerts J, Melkote R, Nuamah I et al. randomized, placebo- and active-controlled study of paliperidone extended-release as maintenance treatment in patients with bipolar I disorder after an acute manic or mixed episode. J Affect Disord 2012; 138: 247-258
    CrossrefPubMedSearch in Google Scholar
  • 16 Pugh MJ, Starner CI, Amuan ME et al. Exposure to potentially harmful drug-disease interactions in older community-dwelling veterans based on the Healthcare Effectiveness Data and Information Set quality measure: who is at risk?. J Am Geriatr Soc 2011; 59: 1673-1678
    CrossrefPubMedSearch in Google Scholar
  • 17 Zhang K, Young C, Berger J. Administrative claims analysis of the relationship between warfarin use and risk of hemorrhage including drug-drug and drug-disease interactions. J Manag Care Pharm 2006; 12: 640-648
    PubMedSearch in Google Scholar
  • 18 Mallet L, Spinewine A, Huang A. The challenge of managing drug interactions in elderly people. Lancet 2007; 370: 185-191
    CrossrefPubMedSearch in Google Scholar
  • 19 Sergi G, De Rui M, Sarti S et al. Polypharmacy in the elderly: can comprehensive geriatric assessment reduce inappropriate medication use?. Drugs Aging 2011; 28: 509-518
    CrossrefPubMedSearch in Google Scholar
  • 20 http://www.tevausa.com/assets/base/products/pi/Divalproex_PI_12-2007.pdf (accessed May 23, 2012
    PubMed