Saliva Versus Plasma Therapeutic Drug Monitoring of Valproic Acid in Jordanian Patients

Abstract

Therapeutic drug monitoring is used to ensure that medications are prescribed and administered according to safe doseage advice and for the purpose of achieving the desired therapeutic effects in patients. Several methods are used to perform therapeutic drug monitoring. However, there is insufficient evidence to currently support therapeutic drug monitoring of Valproic acid using salivary samples. The aim of this paper is to determine the feasibility of using salivary samples as a substitute for plasma samples for therapeutic drug monitoring of Valproic acid. In this study a total of 23 patients participated, with the mean age of 33.39. Salivary and plasma samples were collected and analysed to determine the peak and trough concentrations of Valproic acid for comparison between the two methods. Calibrated LC- MS/ MS was used to measure Valproic acid levels. Statistical analyses were performed using ANOVA test and ethical approval was obtained prior to sample collection. The results showed that saliva Valproic acid levels were less than that of plasma levels. There was no significant correlation between saliva and plasma level of Valproic acid (P>0.05). However, there was a significant correlation between the area under the curve for both saliva and plasma Valproic acid (P<0.05). Creatinine clearance was significantly correlated with peak plasma levels of Valproic acid (P<0.05). Albumin was significantly correlated with plasma levels of Valproic acid. There was also a significantly positive and moderate relationship between Log Saliva Cmax and Log plasma free Valproic acid concentration (r=0.76, p<0.018). In conclusion, saliva samples can be used as a substitute for plasma samples in the therapeutic drug monitoring of Valproic acid.

Keywords

therapeutic drug monitoring - salivary excretion classification system - valproic acid

• References

• 1 Lagace D, O’Brien W, Gurvich N, Nachtigal M, Klein P. Valproic acid: how it works or not. Clinical Neuroscience Research 2004; 4: 215-225
• 2 Abdul-Aziz M, Alffenaar J, Bassetti M, Bracht H, Dimopoulos G. and the 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. Intensive Care Medicine 2020; 46: 1127-1153
• 3 Hiemke C, Bergemann N, Clement H, Conca A, Deckert J, Baumann P. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry 2018; 51: 9-62
• 4 Hutchinson L, Sinclair M, Reid B, Burnett K, Callan B. A descriptive systematic review of salivary therapeutic drug monitoring in neonates and infants. British Journal of Clinical Pharmacology 2018; 84: 1089-1108
• 5 van den Elsen S, Akkerman O, Jongedijk E, Wessels M, Ghimire S, Alffenaar J. Therapeutic drug monitoring using saliva as matrix: an opportunity for linezolid, but challenge for moxifloxacin. European Respiratory Journal 2020; 55: 1901903
• 6 Paci A, Veal G, Bardin C, Leveque D, Widmer N, Chatelut E. Review of therapeutic drug monitoring of anticancer drugs part 1 – cytotoxics. European Journal of Cancer 2014; 50: 2010-2019
• 7 Idkaidek N, Arafat T. Saliva versus plasma pharmacokinetics: theory and application of a salivary excretion classification system. Molecular pharmaceutics 2012; 9: 2358-2363 Kang J. and Lee M. (2009). Overview of therapeutic drug monitoring. Korean Journal of Internal Medicine, 24 (1), 1 – 10
• 8 Singu B, Morrison H, Irengeya L, Verbeeck R. Therapeutic drug monitoring of phenytoin and valproic acid in critically ill patients at Windhoek Central Hospital, Namibia. African Journal of Laboratory Medicine 2022; 11: 1628
• 9 Henry T. The history of valproate in clinical neuroscience. Psychopharmacology Bulletin 2003; 37: 5-16
• 10 Sohn DW, Shin S, Jang I. Pharmacokinetic and Pharmacodynamic Interaction of Lorazepam and Valproic Acid in Relation to UGT2B7 Genetic Polymorphism in Healthy Subjects. Clinical Pharmacology & Therapeutics 2008; 83: 595-600