Saliva as a Noninvasive Biological Sample to Compare Bioavailability of Phenytoin Formulations by LC-MS/MS (original) (raw)

Salivary Biomarkers of Anti-Epileptic Drugs: A Narrative Review

Diagnostics

Saliva is a biofluid that reflects general health and that can be collected in order to evaluate and determine various pathologies and treatments. Biomarker analysis through saliva sampling is an emerging method of accurately screening and diagnosing diseases. Anti-epileptic drugs (AEDs) are prescribed generally in seizure treatment. The dose–response relationship of AEDs is influenced by numerous factors and varies from patient to patient, hence the need for the careful supervision of drug intake. The therapeutic drug monitoring (TDM) of AEDs was traditionally performed through repeated blood withdrawals. Saliva sampling in order to determine and monitor AEDs is a novel, fast, low-cost and non-invasive approach. This narrative review focuses on the characteristics of various AEDs and the possibility of determining active plasma concentrations from saliva samples. Additionally, this study aims to highlight the significant correlations between AED blood, urine and oral fluid levels a...

Salivary free concentrations of anti-epileptic drugs: an evaluation in a routine clinical setting

Acta neurologica Belgica, 2003

This study was aimed at correlating the salivary and serum free concentrations of anti-epileptic drugs (carbamazepine, phenytoin and sodium valproate) in a population of neurological patients in a routine clinical setting. Twenty-seven paired serum/saliva specimens from 22 patients: 10 for carbamazepine, 8 for phenytoin and 9 for sodium valproate were obtained to study these correlations. Salivary and serum free concentrations of anti-epileptic drugs, anti-epileptic drug dosing history, and associated information were collected prospectively. The salivary and serum free concentrations of the anti-epileptic drugs were simultaneously quantified using fluorescence polarization immunoassay (TDx analyzer). For both carbamazepine and phenytoin there was a strong correlation between the salivary and serum free concentrations, 0.99 and 0.98, respectively. The mean ratio of salivary to serum free carbamazepine concentration was 1.02 +/- 0.11 and 0.82 +/- 0.15 for phenytoin. A poor correlatio...

Phenytoin concentration in people with epilepsy: a comparative study in serum and saliva

Pharmacia

In clinical practice, therapeutic drug monitoring (TDM) makes it possible to measure the concentration of drugs in serum or saliva, the purpose of which is to reduce adverse effects and optimize pharmacological therapy. The objective was to determine the concentrations of Phenytoin in saliva and serum of people with epilepsy. Cross-sectional, descriptive study with dynamic recruitment of 30 people with epilepsy (n = 30; 17 men, 56.7% and 13 women, 43.3%; mean age 33.9 ± 11.83 years). Serum and saliva samples were collected at trough levels from patients, who were under phenytoin treatment for at least three months. Drug levels were assessed by the Cloned Donor Enzyme Immunoassay method. Phenytoin levels were found in saliva between 0.01 to 3.56 mg/L and in serum between 0.09 to 36.60 mg/L. Pearson’s analysis showed an association between the estimated serum and saliva phenytoin concentrations (R2 0.7026; 95% CI 0.685-0.921), with a significant statistical correlation (p < 0.05). ...

Use of Saliva as an Alternative Matrix to Serum/Plasma for Therapeutic Drug Monitoring Using Reverse-Phase HPLC

Clinical Therapeutics, 2021

PURPOSE This study was conducted to examine and verify the use of saliva as an alternative matrix for monitoring phenytoin drug levels in patients with epilepsy. Drug concentrations are measured to evaluate whether a suitable drug level has been achieved to minimize the risk for toxicity, inadequate efficacy, or therapy resistance and compliance issues. METHODS Quantitative analysis was performed by using reverse-phase HPLC after sample pretreatment with acetonitrile. Seventy-eight patients who met the inclusion/exclusion criteria were examined in this study. Trough concentrations of both saliva and serum were taken at steady state. FINDINGS Of the 78 patients enrolled, only 11 (14.1%) had normal levels. Twenty-eight patients (35.9%) had subtherapeutic levels, and 39 (50%) had toxic levels. Simultaneously, salivary phenytoin levels were analyzed; only 13 patients (17.3%) had therapeutic levels, 25 patients (33.3%) had subtherapeutic levels, and 37 (49.3%) had toxic levels. Among the study population, most of the patients were aged 31 to 40 years (25.6%) followed by the age group 21 to 30 years (19.2%). The lowest percentage of patients were in the age groups 71 to 80 years and >80 years (1.3%) each. This study found a statistically significant relationship between free serum and salivary phenytoin levels (P < 0.001). A very weak and insignificant correlation was observed between serum/salivary phenytoin levels and sex/age of the study population. The results of the present study support the use of saliva as an alternative to serum/plasma for monitoring phenytoin therapy. IMPLICATIONS The free concentration of a drug represents the freely diffusible drug fraction, which is the therapeutically active form. Accordingly, the free drug concentration correlates to clinical efficacy and drug toxicity better than total concentration.