Saliva versus plasma therapeutic drug monitoring of carbamazepine in Jordanian patients

Year 2024, Volume: 28 Issue: 2, 494 - 504, 28.06.2025

Laith Alshouha , Haya Tuffaha , Aya Al-tarawneh Majed Abdelqader Asma Zinati Ahmad Al-ghazawi , Ayman Rabayah , Salim Hamadi Nasir Idkaidek

Abstract

Therapeutic drug monitoring (TDM) is a helpful method to make sure that drugs are prescribed, delivered, and experienced by patients at the intended therapeutic levels. There are several ways to carry out TDM. The TDM of carbamazepine utilizing salivary samples is not, however, supported by enough data. The aim of this study is to evaluate the possibility of utilizing salivary samples in place of plasma samples for the TDM of carbamazepine. In this study, an observational design was used. Where 14 patients in total took part. For comparison, carbamazepine plasma and salivary samples were taken at maximum and minimum levels. Carbamazepine levels were tested using calibrated LC MS-MS then ANOVA test was used for statistical analysis. Obtaining ethical permission came before sample collection. The minimum plasma and salivary levels concentrations were significantly correlated (p = 0.025, r=0.59). Maximum plasma and salivary levels of carbamazepine concentrations were significantly correlated (p = 0.005, r=0.7). AST was significantly correlated with maximum plasma carbamazepine concentrations (p = 0.036, r = 0.8). No other significant relationships were found between carbamazepine concentrations and sociodemographic characteristics. In conclusion, saliva samples can be used as an alternative to plasma samples while monitoring the therapeutic effects of carbamazepine. Compared to plasma TDM for carbamazepine, salivary TDM offers the benefit of being non-invasive and safer than blood sampling.

Keywords

Salivary excretion classification system , therapeutic drug monitoring , carbamazepine , pk-sim

References

• [1] Bauer LA (Ed.). Applied Clinical Pharmacokinetics, second ed. McGraw Hill, USA. 2008.
• [2] Löscher W, Schmidt D. Modern antiepileptic drug development has failed to deliver: Ways out of the current dilemma. Epilepsia. 2011; 52(4): 657-678. https://doi.org/10.1111/j.1528-1167.2011.03024.x
• [3] Staffs of Lexi-Comp. Clinical Pharmacokinetics Pharmacy Handbook. Medical Books, USA. 2017.
• [4] Leucht S, Samara M, Heres S, Patel MX, Woods SW, Davis JM. Dose equivalents for second-generation antipsychotics: the minimum effective dose method. Schizophrenia Bull. 2014; 40(2): 314-326. https://doi.org/10.1093/schbul/sbu001
• [5] Piscitelli SC. The role of therapeutic drug monitoring in the management of HIV-infected patients. Curr Infect Dis Rep. 2002; 4: 353-358. https://doi.org/10.1007/s11908-002-0028-9
• [6] Abdul-Aziz MH, Alffenaar JWC, Bassetti M, Bracht H, Dimopoulos G, Marriott D, Neely MN, Paiva JA, Pea F, Sjovall F, Timsit JF, Udy AA, Wicha SG, Zeitlinger M, De Waele JJ, Roberts JA, Infection Section of European Society of Intensive Care Medicine (ESICM). Pharmacokinetic/pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Group of International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), Infections in the ICU and Sepsis Working Group of International Society of Antimicrobial Chemotherapy. Antimicrobial therapeutic drug monitoring in critically ill adult patients: a position paper. Intens Care Med. 2002; 46(6): 1127-1153. https://doi.org/10.1007/s00134-020-06050-1
• [7] Burtis CA, Ashwood ER, Bruns DE. Tietz textbook of clinical chemistry and molecular diagnostics. 5th ed. St. Louis, MO: Elsevier Saunders, USA. 2012.
• [8] Landmark JC, Johannessen SI, Patsalos PN. Therapeutic drug monitoring of antiepileptic drugs: current status and future prospects. Expert Opin Drug Metabol Toxicol. 2020; 16(3):227-238. https://doi.org/10.1080/17425255.2020.1724956
• [9] Kang JS, Lee MH. Overview of therapeutic drug monitoring. Korean J Int Med. 2009; 24(1): 1-10. https://doi.org/10.3904/kjim.2009.24.1.1
• [10] Dasgupta A, Therapeutic drug monitoring. In A. Dasgupta (Ed.), Accurate Results in Clinical Laboratories: A Guide to Error Detection and Correction. Elsevier, USA. 2013, pp. 119-144.
• [11] El-Bilbeisi H, Wilson AM. Therapeutic drug monitoring. In: Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook and Computer Simulations. Wiley, USA. 2013.
• [12] Clarke W, Immunoassays for therapeutic drug monitoring and clinical toxicology. In: Handbook of Analytical Separations, Vol. 7. Elsevier BV. 2020, pp. 97-114. https://doi.org/10.1016/B978-0-444-64066-6.00005-8
• [13] Datar PA. Quantitative bioanalytical and analytical method development of dibenzazepine derivative, carbamazepine: A review. J Pharm Anal. 2015; 5(4): 213-222. https://doi.org/10.1016/j.jpha.2015.02.005
• [14] Gaspar VP, Ibrahim S, Zahedi RP, Borchers CH. Utility, promise, and limitations of liquid chromatography-mass spectrometry-based therapeutic drug monitoring in precision medicine. J Mass Spect. 2021; 56(11): e4788. https://doi.org/10.1002/jms.4788
• [15] Punj A. Secretions of Human Salivary Gland. Salivary Glands - New Approaches in Diagnostics and Treatment. IntechOpen, 2019. https://doi.org/10.5772/intechopen.75538
• [16] Bhattarai KR, Kim HR, Chae HJ. Compliance with saliva collection protocol in healthy volunteers: Strategies for managing risk and errors. Int J Med Sci. 2018; 15(8): 823-831. https://doi.org/10.7150/ijms.25146
• [17] Alvarado A, García G, Morales A, Paredes G, Mora M, Muñoz AM, Pariona R, Bendezú MR, Chávez H, García JA, Laos-Anchante D, Loja-Herrera B, Bolarte-Arteaga M, Pineda M. Phenytoin concentration in people with epilepsy: a comparative study in serum and saliva. Pharmacia. 2022; 69(3): 809-814. https://doi.org/10.3897/pharmacia.69.e87168
• [18] Ghareeb M, Gohh RY, Akhlaghi F. Tacrolimus concentration in saliva of kidney transplant recipients: Factors influencing the relationship with whole blood concentrations. Clin Pharmacokinet. 2018; 57(9): 1199-1210. https://doi.org/10.1007/s40262-017-0626-1
• [19] Navazesh M. Methods for collecting saliva. Ann New York Acad Sci. 1993; 694(1): 72-77. https://doi.org/10.1111/j.1749-6632.1993.tb18343.x
• [20] Patsalos PN, Berry DJ. Therapeutic drug monitoring of antiepileptic drugs by use of saliva. Therap Drug Monitor. 2013; 35(1): 4–29. https://doi.org/10.1097/ftd.0b013e31827c11e7
• [21] Idkaidek N, Arafat T. Saliva versus plasma pharmacokinetics: Theory and application of a salivary excretion classification system. Mol Pharmaceutics. 2012; 9(8):2358–2363. https://doi.org/10.1021/mp300250r
• [22] Kovačević I, Parojčić J, Homšek I, Tubić-Grozdanis M, Langguth P. Justification of biowaiver for carbamazepine, a low soluble high permeable compound, in solid dosage forms based on IVIVC and gastrointestinal simulation. Mol Pharmaceutics. 2009; 6(1): 40–47. https://doi.org/10.1021/mp800128y