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Therapeutic Drug Monitoring of Antiepileptic Drugs in Turkey: Five Years’ Experiences

Year 2021, Volume: 43 Issue: 1, 36 - 41, 20.01.2021
https://doi.org/10.20515/otd.767494

Abstract

Therapeutic drug monitoring (TDM) plays a major role in planning and optimizing the treatment of a patient, as in the treatment of epilepsy. The monitoring of antiepileptic drugs (AEDs) in the management of epilepsy is crucial because of their complex pharmacokinetic properties, narrow therapeutic index, and wide fluctuations. In this study, we aimed to investigate the 5-year TDM results of AED, which is one of the most applied groups to our laboratory, in terms of age, gender and plasma concentrations (by therapeutic limit). We also aimed to guide clinicians who diagnose and treat epilepsy patients. This study was conducted to retrospectively analyze the TDM results of patients in Eskişehir Osmangazi University Hospital between 2013-2018. The AED levels were classified as below, within, and above the reference range. The monitored drugs were valproic acid, carbamazepine, phenytoin, phenobarbital, and levetiracetam. The percent of all drug level results analyzed for valproic acid, carbamazepine, levetiracetam and phenobarbital was within the reference range. Phenytoin showed wide fluctuation and its subtherapeutic level was notably high. In practice, TDM was found to be helpful in the of adjustment drug dosage with regard to the response of individual patients.

References

  • 1. Falcicchia C, Simonato M, Verlengia G. New tools for epilepsy therapy. Front Cell Neurosci. 2018 May 29;12:147.
  • 2. Alvarez N, Besag F, Iivanainen M. Use of antiepileptic drugs in the treatment of epilepsy in people with intellectual disability. J Intellect Disabil Res. 1998 Dec;42 Suppl 1:1-15.
  • 3. Heaney DC, Sander JW. Antiepileptic drugs: generic versus branded treatments. Lancet eurol 2007;6(5):465–468.
  • 4. Iapadre G, Balagura G, Zagaroli L, Striano P, Verrotti A. Pharmacokinetics and drug interaction of antiepileptic drugs in children and adolescents. Paediatr Drugs. 2018 Jul 12.
  • 5. Ben Mahmoud L, Hakim A, Ghozzi H, Atheymen R, Sahnoun Z, Zeghal K. Influence of age and co-medication on the steady-state pharmacokinetics of valproic acid in Tunisian patients with epilepsy. Rev Neurol (Paris). 2017 Mar;173(3):159-163.
  • 6. Gogtay NJ, Kshirsagar NA, Dalvi SS. Therapeutic drug monitoring in a developing country: an overview. Br J Clin Pharmacol. 2001;52 Suppl 1:103S-108S.
  • 7. Forooghipour M, Mohammadpour AH, Mashhadian NV, Khayyat MH, Azarpajouh MR, Mokhber N, Aghebati T Shamsara J. Therapeutic Drug Monitoring of Valproic Acid in Patients with Monotherapy at Steady State. Iranian Journal of Basic Medical Sciences. Vol. 12, No. 3-4, Autumn 2009, 146-149.
  • 8. Patsalos PN, Spencer EP, Berry DJ. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: A 2018 Update. Ther Drug Monit. 2018 Oct;40(5):526-548.
  • 9. Aydın O, Ellidag HY, Eren E, Yilmaz N. The laboratory should actively be involved in the therapeutic drug monitoring (TDM) Process. Indian Journal of Pharmacy Practice, Vol 9, Issue 1, Jan-Mar, 2016.
  • 10. Nwobodo N. Therapeutic drug monitoring in a developing nation: a clinical guide. JRSM Open. 2014 Jul 8;5(8):2054270414531121.
  • 11. Yamantürk P, Ozek M, Sevgi S, Eroglu L. Therapeutic drug monitoring in Turkey: experiences from Istanbul. Ther Drug Monit. 2000 Oct;22(5):545-8.
  • 12. Cruz M. M, Ruiz M. E, Romero A. A. C, Robles-Piedras A. L. Appropriateness of Antiepileptic Drug-Level Monitoring at A Childrens' Hospital in Mexico. Biomedical & Pharmacology Journal. 2017 Vol. 10(1), 329-335.
  • 13. Taur SR, Kulkarni NB, Gogtay NJ, Thatte UM. An audit of therapeutic drug monitoring services of anticonvulsants at a tertiary care hospital in India. Ther Drug Monit. 2013 Apr;35(2):183-7.
  • 14. Long PW. Phenytoin: Drug monograph. In: Internet mental health. [Online]1995-2008. [cited: 2019 Jan 11]. Available from: URL: http://www.mentalhealth.com/drug/p30-d05.htm.
  • 15. Adrian MB. Drug interactions that matter. The pharmaceutical Journal 1999; 262 (7035):325-27.
  • 16. Aynacioglu AS, Brockmöller J, Bauer S, et al. Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br J Clin Pharmacol. 2001;48(3):409–415).
  • 17. Liao K, Liu Y, Ai CZ, Yu X, Li W. The association between CYP2C9/2C19 polymorphisms and phenytoin maintenance doses in Asian epileptic patients: A systematic review and meta-analysis. Int J Clin Pharmacol Ther. 2018 Jul;56(7):337-346.
  • 18. St Louis EK. Monitoring antiepileptic drugs: a level-headed approach. Curr Neuropharmacol. 2009 Jun;7(2):115-9

Türkiye’de Antiepileptik İlaçların Terapötik İlaç Düzeyi İzlemi: Beş Yıllık Deneyim

Year 2021, Volume: 43 Issue: 1, 36 - 41, 20.01.2021
https://doi.org/10.20515/otd.767494

Abstract

Terapötik ilaç düzeyi izlemi (TİDİ), epilepsi tedavisinde olduğu gibi bir hastanın tedavisinin planlanmasında ve optimize edilmesinde önemli bir rol oynamaktadır. Epilepsi tedavisinde antiepileptik ilaçların (AEİ) düzeyinin izlenmesi, karmaşık farmakokinetik özellikleri, dar terapötik indeksleri ve geniş fluktuasyonları nedeniyle çok önemlidir. Bu çalışmada laboratuvarımızda en çok uygulanan gruplardan biri olan AEİ'nin 5 yıllık TİDİ sonuçlarını yaş, cinsiyet ve plazma konsantrasyonları açısından (terapötik limtlerine göre) araştırmayı amaçladık. Ayrıca epilepsi hastalarını teşhis ve tedavi eden klinisyenlere rehberlik etmeyi amaçladık. Bu çalışma 2013-2018 yılları arasında Eskişehir Osmangazi Üniversitesi Hastanesi'ndeki hastaların TİDİ sonuçlarını retrospektif olarak analiz etmek için yapıldı. AEİ seviyeleri referans aralığı altında, referans aralığı içinde ve üstünde olarak sınıflandırıldı. İzlenen ilaçlar valproik asit, karbamazepin, fenitoin, fenobarbital ve levetirasetam’dı. Valproik asit, karbamazepin, levetirasetam ve fenobarbital için analiz edilen tüm ilaç seviyesi sonuçları yüzdeleri referans aralığındaydı. Fenitoin geniş fluktuasyon gösterdi ve terapötik düzeyi oldukça yüksekti. Uygulamada, TİDİ'nin, bireysel hastaların cevabında ayarlama yapılmasının ilacın dozajında yardımcı olduğu bulunmuştur.

References

  • 1. Falcicchia C, Simonato M, Verlengia G. New tools for epilepsy therapy. Front Cell Neurosci. 2018 May 29;12:147.
  • 2. Alvarez N, Besag F, Iivanainen M. Use of antiepileptic drugs in the treatment of epilepsy in people with intellectual disability. J Intellect Disabil Res. 1998 Dec;42 Suppl 1:1-15.
  • 3. Heaney DC, Sander JW. Antiepileptic drugs: generic versus branded treatments. Lancet eurol 2007;6(5):465–468.
  • 4. Iapadre G, Balagura G, Zagaroli L, Striano P, Verrotti A. Pharmacokinetics and drug interaction of antiepileptic drugs in children and adolescents. Paediatr Drugs. 2018 Jul 12.
  • 5. Ben Mahmoud L, Hakim A, Ghozzi H, Atheymen R, Sahnoun Z, Zeghal K. Influence of age and co-medication on the steady-state pharmacokinetics of valproic acid in Tunisian patients with epilepsy. Rev Neurol (Paris). 2017 Mar;173(3):159-163.
  • 6. Gogtay NJ, Kshirsagar NA, Dalvi SS. Therapeutic drug monitoring in a developing country: an overview. Br J Clin Pharmacol. 2001;52 Suppl 1:103S-108S.
  • 7. Forooghipour M, Mohammadpour AH, Mashhadian NV, Khayyat MH, Azarpajouh MR, Mokhber N, Aghebati T Shamsara J. Therapeutic Drug Monitoring of Valproic Acid in Patients with Monotherapy at Steady State. Iranian Journal of Basic Medical Sciences. Vol. 12, No. 3-4, Autumn 2009, 146-149.
  • 8. Patsalos PN, Spencer EP, Berry DJ. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: A 2018 Update. Ther Drug Monit. 2018 Oct;40(5):526-548.
  • 9. Aydın O, Ellidag HY, Eren E, Yilmaz N. The laboratory should actively be involved in the therapeutic drug monitoring (TDM) Process. Indian Journal of Pharmacy Practice, Vol 9, Issue 1, Jan-Mar, 2016.
  • 10. Nwobodo N. Therapeutic drug monitoring in a developing nation: a clinical guide. JRSM Open. 2014 Jul 8;5(8):2054270414531121.
  • 11. Yamantürk P, Ozek M, Sevgi S, Eroglu L. Therapeutic drug monitoring in Turkey: experiences from Istanbul. Ther Drug Monit. 2000 Oct;22(5):545-8.
  • 12. Cruz M. M, Ruiz M. E, Romero A. A. C, Robles-Piedras A. L. Appropriateness of Antiepileptic Drug-Level Monitoring at A Childrens' Hospital in Mexico. Biomedical & Pharmacology Journal. 2017 Vol. 10(1), 329-335.
  • 13. Taur SR, Kulkarni NB, Gogtay NJ, Thatte UM. An audit of therapeutic drug monitoring services of anticonvulsants at a tertiary care hospital in India. Ther Drug Monit. 2013 Apr;35(2):183-7.
  • 14. Long PW. Phenytoin: Drug monograph. In: Internet mental health. [Online]1995-2008. [cited: 2019 Jan 11]. Available from: URL: http://www.mentalhealth.com/drug/p30-d05.htm.
  • 15. Adrian MB. Drug interactions that matter. The pharmaceutical Journal 1999; 262 (7035):325-27.
  • 16. Aynacioglu AS, Brockmöller J, Bauer S, et al. Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br J Clin Pharmacol. 2001;48(3):409–415).
  • 17. Liao K, Liu Y, Ai CZ, Yu X, Li W. The association between CYP2C9/2C19 polymorphisms and phenytoin maintenance doses in Asian epileptic patients: A systematic review and meta-analysis. Int J Clin Pharmacol Ther. 2018 Jul;56(7):337-346.
  • 18. St Louis EK. Monitoring antiepileptic drugs: a level-headed approach. Curr Neuropharmacol. 2009 Jun;7(2):115-9
There are 18 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section ORİJİNAL MAKALE
Authors

Ezgi Eroğlu 0000-0002-9878-3431

Nuşin Harmancı 0000-0002-5777-2162

Engin Yıldırım 0000-0001-7089-5418

Başar Sırmagül 0000-0002-3273-5226

Publication Date January 20, 2021
Published in Issue Year 2021 Volume: 43 Issue: 1

Cite

Vancouver Eroğlu E, Harmancı N, Yıldırım E, Sırmagül B. Therapeutic Drug Monitoring of Antiepileptic Drugs in Turkey: Five Years’ Experiences. Osmangazi Tıp Dergisi. 2021;43(1):36-41.


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