A sensitive and selective HPLC method for estimation of lamotrigine in human plasma and saliva: application to plasma-saliva correlation in epileptic patients

Mallayasamy, Surulivelrajan; Karthik, A.; Jain, Tarun; Thiyagu, R; Bhat, Krishnamurthy; Gurumadhavrao, Padma; Devarakonda, Ramakrishna

doi:10.1055/s-0031-1296332

Cited by 6 publications

(3 citation statements)

References 14 publications

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“…53,122,191,[249][250][251][252] However, it is vital that each and every analytical method is fully validated for use with saliva before application with this biological matrix. These include immunoassays and a range of chromatographic procedures.…”

Section: Analysis Of Aeds In Salivamentioning

confidence: 99%

Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Patsalos¹,

Berry²

2013

Therapeutic Drug Monitoring

170

126

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Blood (serum/plasma) antiepileptic drug (AED) therapeutic drug monitoring (TDM) has proven to be an invaluable surrogate marker for individualizing and optimizing the drug management of patients with epilepsy. Since 1989, there has been an exponential increase in AEDs with 23 currently licensed for clinical use, and recently, there has been renewed and extensive interest in the use of saliva as an alternative matrix for AED TDM. The advantages of saliva include the fact that for many AEDs it reflects the free (pharmacologically active) concentration in serum; it is readily sampled, can be sampled repetitively, and sampling is noninvasive; does not require the expertise of a phlebotomist; and is preferred by many patients, particularly children and the elderly. For each AED, this review summarizes the key pharmacokinetic characteristics relevant to the practice of TDM, discusses the use of other biological matrices with particular emphasis on saliva and the evidence that saliva concentration reflects those in serum. Also discussed are the indications for salivary AED TDM, the key factors to consider when saliva sampling is to be undertaken, and finally, a practical protocol is described so as to enable AED TDM to be applied optimally and effectively in the clinical setting. Overall, there is compelling evidence that salivary TDM can be usefully applied so as to optimize the treatment of epilepsy with carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and zonisamide. Salivary TDM of valproic acid is probably not helpful, whereas for clonazepam, eslicarbazepine acetate, felbamate, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin, the data are sparse or nonexistent.

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Section: Analysis Of Aeds In Salivamentioning

confidence: 99%

Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Patsalos¹,

Berry²

2013

Therapeutic Drug Monitoring

170

126

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“…HPLC analysis of plasma and brain tissue samples was performed using an RP-HPLC system (Agilent 1260 Infinity series, Agilent Technologies, Santa Clara, CA, USA) by previously-described methods, 43,44 with some modifications. A C18 reversed-phase analytical column (250 mm ×4.6 mm, ID 5 μm; Agilent, USA) with a C18 guard column (SecurityGuard C18, 4 mm ×3 mm inner diameter (ID); Phenomenex, Torrance, CA, USA) was used for the separation.…”

mentioning

confidence: 99%

Enhanced brain delivery of lamotrigine with Pluronic® P123-based nanocarrier

Liu¹,

Wang²,

Zhou³

et al. 2014

IJN

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Background P-glycoprotein (P-gp) mediated drug efflux across the blood–brain barrier (BBB) is an important mechanism underlying poor brain penetration of certain antiepileptic drugs (AEDs). Nanomaterials, as drug carriers, can overcome P-gp activity and improve the targeted delivery of AEDs. However, their applications in the delivery of AEDs have not been adequately investigated. The objective of this study was to develop a nano-scale delivery system to improve the solubility and brain penetration of the antiepileptic drug lamotrigine (LTG). Methods LTG-loaded Pluronic ® P123 (P123) polymeric micelles (P123/LTG) were prepared by thin-film hydration, and brain penetration capability of the nanocarrier was evaluated. Results The mean encapsulating efficiency for the optimized formulation was 98.07%; drug-loading was 5.63%, and particle size was 18.73 nm. The solubility of LTG in P123/LTG can increase to 2.17 mg/mL, making it available as a solution. The in vitro release of LTG from P123LTG presented a sustained-release property. Compared with free LTG, the LTG-incorporated micelles accumulated more in the brain at 0.5, 1, and 4 hours after intravenous administration in rats. Pretreatment with systemic verapamil increased the rapid brain penetration of free LTG but not P123/LTG. Incorporating another P-gp substrate (Rhodamine 123) into P123 micelles also showed higher efficiency in penetrating the BBB in vitro and in vivo. Conclusion These results indicated that P123 micelles have the potential to overcome the activity of P-gp expressed on the BBB and therefore show potential for the targeted delivery of AEDs. Future studies are necessary to further evaluate the appropriateness of the nanocarrier to enhance the efficacy of AEDs.

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“…The authors concluded that, with appropriate timing in sampling, saliva could provide a good alternative for lamotrigine TDM [72]. Incecayir et al also reported a good lamotrigine saliva/serum correlation of r 2 = 0.677, while Mallayasamy et al and Kuczynska et al reported values of r 2 = 0.683 and, respectively, r 2 = 0.82 [70,73,74]. Ryan et al reported good lamotrigine salivary and serum concentrations (r 2 = 0.81-0.84) in both patients under 16 years of age and also adults [75].…”

Section: Lamotriginementioning

confidence: 98%

Salivary Biomarkers of Anti-Epileptic Drugs: A Narrative Review

et al. 2023

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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 and the applicability of saliva TDM for AEDs. The study also focuses on emphasizing the applicability of saliva sampling for epileptic patients.

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A sensitive and selective HPLC method for estimation of lamotrigine in human plasma and saliva: application to plasma-saliva correlation in epileptic patients

Cited by 6 publications

References 14 publications

Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Enhanced brain delivery of lamotrigine with Pluronic® P123-based nanocarrier

Salivary Biomarkers of Anti-Epileptic Drugs: A Narrative Review

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A sensitive and selective HPLC method for estimation of lamotrigine in human plasma and saliva: application to plasma-saliva correlation in epileptic patients

Cited by 6 publications

References 14 publications

Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Enhanced brain delivery of lamotrigine with Pluronic&reg; P123-based nanocarrier

Salivary Biomarkers of Anti-Epileptic Drugs: A Narrative Review

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Product

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Enhanced brain delivery of lamotrigine with Pluronic® P123-based nanocarrier