Research Article
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Evaluation of Serum Drug Concentrations in a Tertiary Care Hospital: A Cross-Sectional Study

Year 2024, Volume: 8 Issue: 1, 143 - 151, 31.01.2024
https://doi.org/10.30621/jbachs.1326233

Abstract

Background: Serum drug concentration (SDC) is an important parameter used in drug efficacy and treatment follow-up.
Aim: This study aimed to evaluate SDC and the influencing factors for carbamazepine, phenytoin, phenobarbital, lithium and digoxin.
Materials and Methods: This is a cross-sectional study, evaluating the outpatients’ and inpatients’ SDC data treated at Research and Application Hospital of Afyonkarahisar Health Sciences University between January 1, 2012 and December 31, 2019, and having SDC data. The relations between dependent and independent variables was evaluated with chi-square analysis and Students’ T-test. P<0.05 was considered statistically significant.
Results: A total of 3735 patients, 8946 admissions (mean: 41.1±26.6 years, 51.3% females) and 10158 SDCs were reviewed. Digoxin SDC was the most common measurement, at a rate of 33.7%. The highest number of SDC measurement was made in 2016 (n=1627). Subtherapeutic SDC rates were high for phenytoin, lithium, and digoxin (69.8%, 39.7%, 35.8%, respectively). Digoxin (16.2%) and phenobarbital (9.8%) were the drugs with the highest rate of toxic SDC. SDC increased for all drugs with increasing age, this was statistically significant for carbamazepine, lithium and digoxin (p<0.05). SDC for digoxin was found to be significantly higher in female gender (p<0.001).
Conclusion: It was concluded in the study that high subtherapeutic and toxic levels detected may result in treatment failure, poor prognosis, longer hospital stay, increased mortality and health expenditures.This study revealed the need for prospective studies evaluating Therapeutic Drug Monitoring (TDM) together with patient- and drug-related factors.

References

  • Helland A, Berg JA, Gustavsen I, Nordal K, Hilberg T, Aronsen L, Arnestad M, Narum S. Serum concentration measurements of addictive drugs. Tidsskr Nor Laegeforen 2016;136(5):400-2.
  • Hiemke C, Bergemann N, Clement HW, et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry 2018;51(1-02):9-62.
  • Basalingappa S, Sharma A, Amarnath S. Basic concepts of therapeutic drug monitoring. Int J Current Pharm 2014;5(4):70-75.
  • Hazarika I. Therapeutic drug monitoring (TDM): an aspect of clinical pharmacology and pharmacy practice. Ther Drug Monit 2015;5(3):27-34.
  • Kang JS, Lee MH. Overview of therapeutic drug monitoring. Korean J Intern Med. 2009;24(1):1-10.
  • Karaalp A, Demir D, Gören MZ, Akc A, ISkender E, Yananl HR, Ozyurt H, Ozkaynakç A, Berkman K, Oktay S, Onat F. Therapeutic drug monitoring of immunosuppressant drugs in Marmara University Hospital. Ther Drug Monit 2004;26(3):263-6.
  • Yamantürk P, Ozek M, Sevgi S, Eroglu L. Therapeutic drug monitoring in Turkey: experiences from Istanbul. Ther Drug Monit 2000;22(5):545-8.
  • Ozunal ZG, Ongen İpek B. Therapeutic Drug Monitoring Characteristics in a Tertiary University Hospital in 2019. Cureus 2020;12(4):e7612.
  • Goldberger ZD, Goldberger AL. Therapeutic ranges of serum digoxin concentrations in patients with heart failure. Am J Cardiol 2012;109(12):1818-1821.
  • Ozyigit F, Kocak FE, Arikan I, Genc O. A retrospective analysis about the quality of therapeutic drug monitoring of digoxin. Sch Acad J Pharm 2015;4(6):331-336.
  • Yilmaz I, Bilgili S, Bozkaya G. Evaluation of digoxin levels in elderly patients in a training hospital: an 11-year follow-up. Turkish Journal of Geriatrics 2020;23(1):108-117.
  • Karaalp A, Akici A, Gören MZ, Berkman K, Onat F. Therapeutic drug monitorıng of antiepileptic drugs in Marmara University Hospital: a three-year follow-up. Pharmacologyonline 2006;2:22-32.
  • Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336(8):525-33.
  • Malik A, Masson R, Singh S, Wu WC, Packer M, Pitt B, Waagstein F, Morgan CJ, Allman RM, Fonarow GC, Ahmed A. Digoxin Discontinuation and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction. J Am Coll Cardiol 2019;74(5):617-627.
  • Pressler RM, Abend NS, Auvin S, et al. Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-Special report from the ILAE Task Force on Neonatal Seizures. Epilepsia 2023;64(10):2550-2570.
  • Grinspan ZM, Shellhaas RA, Coryell J, et al. Comparative Effectiveness of Levetiracetam vs Phenobarbital for Infantile Epilepsy. JAMA Pediatr 2018;172(4):352–360.
  • Sun M, Herrmann N, Shulman KI. Lithium Toxicity in Older Adults: a Systematic Review of Case Reports. Clin Drug Investig 2018;38(3):201-209.
  • Burt M, Anderson DC, Kloss J, Apple FS. Evidence-based implementation of free phenytoin therapeutic drug monitoring. Clin Chem 2000;46:1132-5.
  • Adil M, Farhat S, Rather MY. Therapeutic drug monitoring of phenytoin using high performance liquid chromatography in a tertiary care hospital of Kashmir, India. Int J Basic Clin Pharmacol 2019;8:995-9.
  • Wu MF, Lim WH. Phenytoin: A Guide to Therapeutic Drug Monitoring. Proceedings of Singapore Healthcare 2013:198-202.
  • von Winckelmann SL, Spriet I, Willems L. Therapeutic drug monitoring of phenytoin in critically ill patients. Pharmacotherapy 2008;28(11):1391-400.
  • Dahiya K, Bansal P, Ghalaut VS, Dhankhar R, Ghalaut PS. Therapeutic drug monitoring for antiepileptic drugs using HPLC: an experience at a tertiary care hospital in India. Neurol Asia 2010;15(3):233.
  • Nepal S, Sarraf D, Baral D, Mishra S, Chaudhari R, Sapkota N. Association of Plasma Level of Lithium with Clinical Effect in Bipolar Disorder at a Tertiary Center in Eastern Nepal. Journal of Psychiatrists’ Association of Nepal 2020;9(2):23–29.
  • Sharma S, Joshi S, Chadda RK. Therapeutic drug monitoring of lithium in patients with bipolar affective disorder: experiences from a tertiary care hospital in India. Am J Ther 2009;16(5):393-7. Carli M, Risaliti E, Francomano M, Kolachalam S, Longoni B, Bocci G, Maggio R, Scarselli M. A 5-Year Study of Lithium and Valproic Acid Drug Monitoring in Patients with Bipolar Disorders in an Italian Clinical Center. Pharmaceuticals (Basel) 2022;15(1):105.
  • Devanand DP, Crocco E, Forester BP, Husain MM, Lee S, Vahia IV, Andrews H, Simon-Pearson L, Imran N, Luca L, Huey ED, Deliyannides DA, Pelton GH. Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease: Lit-AD Randomized Clinical Trial. Am J Geriatr Psychiatry 2022;30(1):32-42.
  • Gadh S. Low-dose lithium impact in an addiction treatment setting. Personalized Medicine in Psychiatry 2020;21:100059.
  • Mitchell PB. Therapeutic drug monitoring of psychotropic medications. Br J Clin Pharmacol 2000;49(4):303-12.
  • Severus WE, Kleindienst N, Seemüller F, Frangou S, Möller HJ, Greil W. What is the optimal serum lithium level in the long-term treatment of bipolar disorder--a review? Bipolar Disord 2008;10(2):231-7.
  • Nierenberg AA, Friedman ES, Bowden CL, et al. Lithium treatment moderate-dose use study (LiTMUS) for bipolar disorder: a randomized comparative effectiveness trial of optimized personalized treatment with and without lithium. Am J Psychiatry 2013;170(1):102-10.
  • Hopkins HS, Gelenberg AJ. Serum lithium levels and the outcome of maintenance therapy of bipolar disorder. Bipolar Disord 2000;2:174-9.
  • McDonagh TA, Metra M, Adamo M, et al. ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42(36):3599-3726.
  • Adams KF Jr, Butler J, Patterson JH, et al. Dose response characterization of the association of serum digoxin concentration with mortality outcomes in the Digitalis Investigation Group trial. Eur J Heart Fail 2016;18(8):1072-1081.
  • Rathore SS, Curtis JP, Wang Y, Bristow MR, Krumholz HM. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA 2003;289(7):871-878.
  • Adams KF Jr, Gheorghiade M, Uretsky BF, Patterson JH, Schwartz TA, Young JB. Clinical benefits of low serum digoxin concentrations in heart failure. J Am Coll Cardiol 2002;39(6):946-953.
  • Oncu S, Baskurt A, Senturk B, Aslan O, Kume T, Ucku R, Gelal A. Educational intervention to improve appropriate digoxin therapeutic drug monitoring: a quasi-experimental study. Eur J Hosp Pharm 2021;28(6):320-324.
  • Vella J, Wirth F, Azzopardi LM, Serracino-Inglott A. Serum digoxin concentrations: a retrospective analysis. Pharmacol Cln Toxicol 2018;6:1129.
  • Ragab AR, Al-Mazroua MK, Abdel-Rahman RH. Clinical utility of serum digoxin level in cardiac patients for diagnosis of chronic digitalis toxicity. J Clinic Toxicol 2012;2(150):2161-0495.
  • El-Dib M, Soul JS. The use of phenobarbital and other anti-seizure drugs in newborns. Semin Fetal Neonatal Med 2017;22(5):321-327.
  • Methaneethorn J, Leelakanok N. Pharmacokinetic variability of phenobarbital: a systematic review of population pharmacokinetic analysis. Eur J Clin Pharmacol 2021;77(3):291-309.
  • Perucca E. Treatment of epilepsy in developing countries. BMJ 2007;334:1175-6.
  • Grześk G, Stolarek W, Kasprzak M, et al. Therapeutic drug monitoring of digoxin-20 years of experience. Pharmacol Rep 2018;70(1):184-189.
  • van Melick EJ, Souverein PC, den Breeijen JH, Tusveld CE, Egberts TC, Wilting I. Age as a determinant of instability of serum lithium concentrations. Ther Drug Monit 2013;35(5):643-8.
  • Soldin OP, Mattison DR. Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet 2009;48(3):143-157.
  • Lonsdale DO, Baker EH. Understanding and managing medication in elderly people. Best Pract Res Clin Obstet Gynaecol 2013;27(5):767-788.

Evaluation of Serum Drug Concentrations in a Tertiary Care Hospital: A Cross-Sectional Study

Year 2024, Volume: 8 Issue: 1, 143 - 151, 31.01.2024
https://doi.org/10.30621/jbachs.1326233

Abstract

Supporting Institution

Destek alınmamıştır.

References

  • Helland A, Berg JA, Gustavsen I, Nordal K, Hilberg T, Aronsen L, Arnestad M, Narum S. Serum concentration measurements of addictive drugs. Tidsskr Nor Laegeforen 2016;136(5):400-2.
  • Hiemke C, Bergemann N, Clement HW, et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry 2018;51(1-02):9-62.
  • Basalingappa S, Sharma A, Amarnath S. Basic concepts of therapeutic drug monitoring. Int J Current Pharm 2014;5(4):70-75.
  • Hazarika I. Therapeutic drug monitoring (TDM): an aspect of clinical pharmacology and pharmacy practice. Ther Drug Monit 2015;5(3):27-34.
  • Kang JS, Lee MH. Overview of therapeutic drug monitoring. Korean J Intern Med. 2009;24(1):1-10.
  • Karaalp A, Demir D, Gören MZ, Akc A, ISkender E, Yananl HR, Ozyurt H, Ozkaynakç A, Berkman K, Oktay S, Onat F. Therapeutic drug monitoring of immunosuppressant drugs in Marmara University Hospital. Ther Drug Monit 2004;26(3):263-6.
  • Yamantürk P, Ozek M, Sevgi S, Eroglu L. Therapeutic drug monitoring in Turkey: experiences from Istanbul. Ther Drug Monit 2000;22(5):545-8.
  • Ozunal ZG, Ongen İpek B. Therapeutic Drug Monitoring Characteristics in a Tertiary University Hospital in 2019. Cureus 2020;12(4):e7612.
  • Goldberger ZD, Goldberger AL. Therapeutic ranges of serum digoxin concentrations in patients with heart failure. Am J Cardiol 2012;109(12):1818-1821.
  • Ozyigit F, Kocak FE, Arikan I, Genc O. A retrospective analysis about the quality of therapeutic drug monitoring of digoxin. Sch Acad J Pharm 2015;4(6):331-336.
  • Yilmaz I, Bilgili S, Bozkaya G. Evaluation of digoxin levels in elderly patients in a training hospital: an 11-year follow-up. Turkish Journal of Geriatrics 2020;23(1):108-117.
  • Karaalp A, Akici A, Gören MZ, Berkman K, Onat F. Therapeutic drug monitorıng of antiepileptic drugs in Marmara University Hospital: a three-year follow-up. Pharmacologyonline 2006;2:22-32.
  • Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336(8):525-33.
  • Malik A, Masson R, Singh S, Wu WC, Packer M, Pitt B, Waagstein F, Morgan CJ, Allman RM, Fonarow GC, Ahmed A. Digoxin Discontinuation and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction. J Am Coll Cardiol 2019;74(5):617-627.
  • Pressler RM, Abend NS, Auvin S, et al. Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-Special report from the ILAE Task Force on Neonatal Seizures. Epilepsia 2023;64(10):2550-2570.
  • Grinspan ZM, Shellhaas RA, Coryell J, et al. Comparative Effectiveness of Levetiracetam vs Phenobarbital for Infantile Epilepsy. JAMA Pediatr 2018;172(4):352–360.
  • Sun M, Herrmann N, Shulman KI. Lithium Toxicity in Older Adults: a Systematic Review of Case Reports. Clin Drug Investig 2018;38(3):201-209.
  • Burt M, Anderson DC, Kloss J, Apple FS. Evidence-based implementation of free phenytoin therapeutic drug monitoring. Clin Chem 2000;46:1132-5.
  • Adil M, Farhat S, Rather MY. Therapeutic drug monitoring of phenytoin using high performance liquid chromatography in a tertiary care hospital of Kashmir, India. Int J Basic Clin Pharmacol 2019;8:995-9.
  • Wu MF, Lim WH. Phenytoin: A Guide to Therapeutic Drug Monitoring. Proceedings of Singapore Healthcare 2013:198-202.
  • von Winckelmann SL, Spriet I, Willems L. Therapeutic drug monitoring of phenytoin in critically ill patients. Pharmacotherapy 2008;28(11):1391-400.
  • Dahiya K, Bansal P, Ghalaut VS, Dhankhar R, Ghalaut PS. Therapeutic drug monitoring for antiepileptic drugs using HPLC: an experience at a tertiary care hospital in India. Neurol Asia 2010;15(3):233.
  • Nepal S, Sarraf D, Baral D, Mishra S, Chaudhari R, Sapkota N. Association of Plasma Level of Lithium with Clinical Effect in Bipolar Disorder at a Tertiary Center in Eastern Nepal. Journal of Psychiatrists’ Association of Nepal 2020;9(2):23–29.
  • Sharma S, Joshi S, Chadda RK. Therapeutic drug monitoring of lithium in patients with bipolar affective disorder: experiences from a tertiary care hospital in India. Am J Ther 2009;16(5):393-7. Carli M, Risaliti E, Francomano M, Kolachalam S, Longoni B, Bocci G, Maggio R, Scarselli M. A 5-Year Study of Lithium and Valproic Acid Drug Monitoring in Patients with Bipolar Disorders in an Italian Clinical Center. Pharmaceuticals (Basel) 2022;15(1):105.
  • Devanand DP, Crocco E, Forester BP, Husain MM, Lee S, Vahia IV, Andrews H, Simon-Pearson L, Imran N, Luca L, Huey ED, Deliyannides DA, Pelton GH. Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease: Lit-AD Randomized Clinical Trial. Am J Geriatr Psychiatry 2022;30(1):32-42.
  • Gadh S. Low-dose lithium impact in an addiction treatment setting. Personalized Medicine in Psychiatry 2020;21:100059.
  • Mitchell PB. Therapeutic drug monitoring of psychotropic medications. Br J Clin Pharmacol 2000;49(4):303-12.
  • Severus WE, Kleindienst N, Seemüller F, Frangou S, Möller HJ, Greil W. What is the optimal serum lithium level in the long-term treatment of bipolar disorder--a review? Bipolar Disord 2008;10(2):231-7.
  • Nierenberg AA, Friedman ES, Bowden CL, et al. Lithium treatment moderate-dose use study (LiTMUS) for bipolar disorder: a randomized comparative effectiveness trial of optimized personalized treatment with and without lithium. Am J Psychiatry 2013;170(1):102-10.
  • Hopkins HS, Gelenberg AJ. Serum lithium levels and the outcome of maintenance therapy of bipolar disorder. Bipolar Disord 2000;2:174-9.
  • McDonagh TA, Metra M, Adamo M, et al. ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42(36):3599-3726.
  • Adams KF Jr, Butler J, Patterson JH, et al. Dose response characterization of the association of serum digoxin concentration with mortality outcomes in the Digitalis Investigation Group trial. Eur J Heart Fail 2016;18(8):1072-1081.
  • Rathore SS, Curtis JP, Wang Y, Bristow MR, Krumholz HM. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA 2003;289(7):871-878.
  • Adams KF Jr, Gheorghiade M, Uretsky BF, Patterson JH, Schwartz TA, Young JB. Clinical benefits of low serum digoxin concentrations in heart failure. J Am Coll Cardiol 2002;39(6):946-953.
  • Oncu S, Baskurt A, Senturk B, Aslan O, Kume T, Ucku R, Gelal A. Educational intervention to improve appropriate digoxin therapeutic drug monitoring: a quasi-experimental study. Eur J Hosp Pharm 2021;28(6):320-324.
  • Vella J, Wirth F, Azzopardi LM, Serracino-Inglott A. Serum digoxin concentrations: a retrospective analysis. Pharmacol Cln Toxicol 2018;6:1129.
  • Ragab AR, Al-Mazroua MK, Abdel-Rahman RH. Clinical utility of serum digoxin level in cardiac patients for diagnosis of chronic digitalis toxicity. J Clinic Toxicol 2012;2(150):2161-0495.
  • El-Dib M, Soul JS. The use of phenobarbital and other anti-seizure drugs in newborns. Semin Fetal Neonatal Med 2017;22(5):321-327.
  • Methaneethorn J, Leelakanok N. Pharmacokinetic variability of phenobarbital: a systematic review of population pharmacokinetic analysis. Eur J Clin Pharmacol 2021;77(3):291-309.
  • Perucca E. Treatment of epilepsy in developing countries. BMJ 2007;334:1175-6.
  • Grześk G, Stolarek W, Kasprzak M, et al. Therapeutic drug monitoring of digoxin-20 years of experience. Pharmacol Rep 2018;70(1):184-189.
  • van Melick EJ, Souverein PC, den Breeijen JH, Tusveld CE, Egberts TC, Wilting I. Age as a determinant of instability of serum lithium concentrations. Ther Drug Monit 2013;35(5):643-8.
  • Soldin OP, Mattison DR. Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet 2009;48(3):143-157.
  • Lonsdale DO, Baker EH. Understanding and managing medication in elderly people. Best Pract Res Clin Obstet Gynaecol 2013;27(5):767-788.
There are 44 citations in total.

Details

Primary Language English
Subjects Clinical Sciences (Other)
Journal Section Research Article
Authors

Merve Becit-kızılkaya 0000-0002-8084-4419

Seyma Oncu 0000-0003-2468-2416

Dilek Çavuşoğlu 0000-0003-4924-5300

Halit Buğra Koca 0000-0002-5353-3228

Early Pub Date January 31, 2024
Publication Date January 31, 2024
Submission Date July 12, 2023
Published in Issue Year 2024 Volume: 8 Issue: 1

Cite

APA Becit-kızılkaya, M., Oncu, S., Çavuşoğlu, D., Koca, H. B. (2024). Evaluation of Serum Drug Concentrations in a Tertiary Care Hospital: A Cross-Sectional Study. Journal of Basic and Clinical Health Sciences, 8(1), 143-151. https://doi.org/10.30621/jbachs.1326233
AMA Becit-kızılkaya M, Oncu S, Çavuşoğlu D, Koca HB. Evaluation of Serum Drug Concentrations in a Tertiary Care Hospital: A Cross-Sectional Study. JBACHS. January 2024;8(1):143-151. doi:10.30621/jbachs.1326233
Chicago Becit-kızılkaya, Merve, Seyma Oncu, Dilek Çavuşoğlu, and Halit Buğra Koca. “Evaluation of Serum Drug Concentrations in a Tertiary Care Hospital: A Cross-Sectional Study”. Journal of Basic and Clinical Health Sciences 8, no. 1 (January 2024): 143-51. https://doi.org/10.30621/jbachs.1326233.
EndNote Becit-kızılkaya M, Oncu S, Çavuşoğlu D, Koca HB (January 1, 2024) Evaluation of Serum Drug Concentrations in a Tertiary Care Hospital: A Cross-Sectional Study. Journal of Basic and Clinical Health Sciences 8 1 143–151.
IEEE M. Becit-kızılkaya, S. Oncu, D. Çavuşoğlu, and H. B. Koca, “Evaluation of Serum Drug Concentrations in a Tertiary Care Hospital: A Cross-Sectional Study”, JBACHS, vol. 8, no. 1, pp. 143–151, 2024, doi: 10.30621/jbachs.1326233.
ISNAD Becit-kızılkaya, Merve et al. “Evaluation of Serum Drug Concentrations in a Tertiary Care Hospital: A Cross-Sectional Study”. Journal of Basic and Clinical Health Sciences 8/1 (January 2024), 143-151. https://doi.org/10.30621/jbachs.1326233.
JAMA Becit-kızılkaya M, Oncu S, Çavuşoğlu D, Koca HB. Evaluation of Serum Drug Concentrations in a Tertiary Care Hospital: A Cross-Sectional Study. JBACHS. 2024;8:143–151.
MLA Becit-kızılkaya, Merve et al. “Evaluation of Serum Drug Concentrations in a Tertiary Care Hospital: A Cross-Sectional Study”. Journal of Basic and Clinical Health Sciences, vol. 8, no. 1, 2024, pp. 143-51, doi:10.30621/jbachs.1326233.
Vancouver Becit-kızılkaya M, Oncu S, Çavuşoğlu D, Koca HB. Evaluation of Serum Drug Concentrations in a Tertiary Care Hospital: A Cross-Sectional Study. JBACHS. 2024;8(1):143-51.