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Assessment of Antiepileptic Drug Concentrations in HIV-Infected versus HIV-Negative Patients: A Retrospective Analysis

  • Dario Cattaneo
  • Sara Baldelli
  • Andrea Giacomelli
  • Davide Minisci
  • Paola Meraviglia
  • Noemi Astuti
  • Marta Fusi
  • Valeria Cozzi
  • Emilio Clementi
  • Massimo Galli
  • Cristina GervasoniEmail author
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Abstract

Introduction

A higher rate of subtherapeutic psychotropic drug concentrations was recently found in HIV-infected versus HIV-negative patients. In this study, we sought to investigate if this trend could also apply to antiepileptic drugs.

Methods

Overall, 700 HIV-infected patients were screened during the first 2 years after the introduction of our outpatient polytherapy management service (Gestione Ambulatoriale Politerapie [GAP]) in the search for subjects with antiepileptic drug trough concentration assessments. The distribution of such concentrations was compared with that in HIV-negative patients monitored over the same period.

Results

The search identified 97 HIV-infected patients concomitantly receiving antiretroviral and antiepileptic drugs, for a total of 310 drug measurements. Overall, 30%, 64% and 6%, versus 28%, 65% and 7%, of the antiepileptic concentrations measured in HIV-infected versus HIV-negative patients (1090 patients, for a total of 3488 antiepileptic concentrations measured) were below, within, or above the therapeutic targets, respectively. The antiepileptic drug valproate was associated with the highest risk of subtherapeutic drug concentrations, with 57% and 46% of determinations below the therapeutic range in HIV-positive and HIV-negative patients, respectively. Remarkably, the concentrations of valproate were significantly lower in HIV-infected versus HIV-negative patients (47.9 ± 21.2 versus 53.9 ± 21.6 mg/L; p < 0.05).

Conclusion

In our retrospective study, most HIV-infected patients had antiepileptic drug concentrations falling within the therapeutic targets, with the exception of valproate, which was associated with a higher rate of subtherapeutic concentrations compared with other antiepileptic drugs.

Notes

Funding

This study was carried out as part of our routine work, and no external funds were used.

Compliance with Ethical Standards

Conflicts of interest

Cristina Gervasoni and Massimo Galli have received educational grants from Merck Sharp & Dohme (MSD), Janssen-Cilag, Bristol Myers Squibb, Boehringer Ingelheim, ViiV Healthcare and Abbvie. Paola Meraviglia has received educational grants from Merck Sharp & Dohme (MSD), Janssen-Cilag, Bristol Myers Squibb, Boehringer Ingelheim and ViiV Healthcare. Dario Cattaneo has received educational and travel grants from Merck Sharp & Dohme (MSD) and ViiV Healthcare. Sara Baldelli, Andrea Giacomelli, Davide Minisci, Noemi Astuti, Marta Fusi, Valeria Cozzi, and Emilio Clementi declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript.

References

  1. 1.
    Stefanović S, Janković SM, Novaković M, Milosavljević M, Folić M. Pharmacodynamics and common drug-drug interactions of the third-generation antiepileptic drugs. Expert Opin Drug Metab Toxicol. 2018;14:153–9.CrossRefGoogle Scholar
  2. 2.
    Zaccara G, Perucca E. Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs. Epileptic Disord. 2014;16:409–31.Google Scholar
  3. 3.
    Patsalos PN. Drug interactions with the newer antiepileptic drugs (AEDs)—part 2: pharmacokinetic and pharmacodynamic interactions between AEDs and drugs used to treat non-epilepsy disorders. Clin Pharmacokinet. 2013;52:1045–61.CrossRefGoogle Scholar
  4. 4.
    Patsalos PN. Drug interactions with the newer antiepileptic drugs (AEDs)—part 1: pharmacokinetic and pharmacodynamic interactions between AEDs. Clin Pharmacokinet. 2013;52:927–66.CrossRefGoogle Scholar
  5. 5.
    Birbeck GL, French JA, Perucca E, Simpson DM, Fraimow H, George JM, Quality Standards Subcommittee of the American Academy Of Neurology, Ad Hoc Task Force of the Commission on Therapeutic Strategies of the International League Against Epilepsy, et al. Antiepileptic drug selection for people with HIV/AIDS: evidence-based guidelines from the ILAE and AAN. Epilepsia. 2012;53:207–14.CrossRefGoogle Scholar
  6. 6.
    Sarma AK, Khandker N, Kurczewski L, Brophy GM. Medical management of epileptic seizures: challenges and solutions. Neuropsychiatr Dis Treat. 2016;12:467–85.Google Scholar
  7. 7.
    Kirmani BF, Mungall-Robinson D. Role of anticonvulsants in the management of AIDS related seizures. Front Neurol. 2014;5:10.Google Scholar
  8. 8.
    Liedtke MD, Lockhart SM, Rathbun RC. Anticonvulsant and antiretroviral interactions. Ann Pharmacother. 2004;38:482–9.CrossRefGoogle Scholar
  9. 9.
    Romanelli F, Pomeroy C. Concurrent use of antiretrovirals and anticonvulsants in human immunodeficiency virus (HIV) seropositive patients. Curr Pharm Des. 2003;9:1433–9.CrossRefGoogle Scholar
  10. 10.
    Hiemke C, Bergemann N, Clement HW, Conca A, Deckert J, Domschke K, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry. 2018;51:9–62.CrossRefGoogle Scholar
  11. 11.
    Cattaneo D, Baldelli S, Resnati C, Giacomelli A, Meraviglia P, Minisci D, et al. Evaluation of the concentrations of psychotropic drugs in HIV-infected versus HIV-negative patients: potential implications for clinical practice. World J Biol Psychiatry. 2018.  https://doi.org/10.1080/15622975.2018.1500032 (Epub 20 Sep 2018).Google Scholar
  12. 12.
    Baldelli S, Cattaneo D, Giodini L, Baietto L, Di Perri G, D’Avolio A, et al. Development and validation of a HPLC-UV method for the quantification of antiepileptic drugs in dried plasma spots. Clin Chem Lab Med. 2015;53:435–44.CrossRefGoogle Scholar
  13. 13.
    Jacob S, Nair AB. An updated overview on therapeutic drug monitoring of recent antiepileptic drugs. Drugs R D. 2016;16:303–16.CrossRefGoogle Scholar
  14. 14.
    Landmark CJ, Johannessen SI, Tomson T. Dosing strategies for antiepileptic drugs: from a standard dose for all to individualised treatment by implementation of therapeutic drug monitoring. Epileptic Disord. 2016;18:367–83.Google Scholar
  15. 15.
    Eadie MJ. Therapeutic drug monitoring: antiepileptic drugs. Br J Clin Pharmacol. 2001;52(Suppl 1):11S–20S.CrossRefGoogle Scholar
  16. 16.
    Mandrioli R, Protti M, Mercolini L. Novel atypical antipsychotics: metabolism and therapeutic drug monitoring (TDM). Curr Drug Metab. 2015;16:141–51.CrossRefGoogle Scholar
  17. 17.
    Grundmann M, Kacirova I, Urinovska R. Therapeutic drug monitoring of atypical antipsychotic drugs. Acta Pharm. 2014;64:387–401.CrossRefGoogle Scholar
  18. 18.
    Patteet L, Morrens M, Maudens KE, Niemegeers P, Sabbe B, Neels H. Therapeutic drug monitoring of common antipsychotics. Ther Drug Monit. 2012;34:629–51.CrossRefGoogle Scholar
  19. 19.
    Palazzo A, Trunfio M, Pirriatore V, Milesi M, De Nicolò A, Alcantarini C, et al. Lower dolutegravir plasma concentrations in HIV-positive patients receiving valproic acid. J Antimicrob Chemother. 2018;73(3):826–7.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Dario Cattaneo
    • 1
    • 2
  • Sara Baldelli
    • 2
  • Andrea Giacomelli
    • 3
  • Davide Minisci
    • 3
  • Paola Meraviglia
    • 3
  • Noemi Astuti
    • 3
  • Marta Fusi
    • 2
  • Valeria Cozzi
    • 2
  • Emilio Clementi
    • 4
    • 5
  • Massimo Galli
    • 3
  • Cristina Gervasoni
    • 1
    • 3
    • 6
    Email author
  1. 1.Gestione Ambulatoriale Politerapie (GAP) Outpatient ClinicASST Fatebenefratelli SaccoMilanItaly
  2. 2.Unit of Clinical PharmacologyASST Fatebenefratelli SaccoMilanItaly
  3. 3.Department of Infectious DiseasesASST Fatebenefratelli SaccoMilanItaly
  4. 4.Clinical Pharmacology Unit, Department of Biomedical and Clinical SciencesConsiglio Nazionale delle Ricerche Institute of Neuroscience, Sacco University Hospital, Università degli Studi di MilanoMilanItaly
  5. 5.E. Medea Scientific InstituteBosisio PariniItaly
  6. 6.Department of Infectious DiseasesLuigi Sacco University HospitalMilanItaly

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