Concentrations of Zonisamide in Serum, Free Fraction, Mixed Saliva and Cerebrospinal Fluid in Epileptic Children Treated with Monotherapy

Kumagai, Noboru; Seki, Tohru; Yamada, Tetsuya; Takuma, Yuuichi; Hirai, Kenichiro

doi:10.1111/j.1440-1819.1993.tb02077.x

Cited by 8 publications

(7 citation statements)

References 1 publication

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“…80 More recently, Jones et al 186 included saliva samples from patients prescribed zonisamide in a mailing stability study, and although they demonstrated that the drug was stable in saliva, the authors did not compare the individual results with matching serum specimens. The drug seems to be actively secreted into saliva because concentrations are reported to be higher than the free concentration in serum.…”

Section: Saliva Tdm For Zonisamidementioning

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: Saliva Tdm For Zonisamidementioning

confidence: 99%

Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Patsalos¹,

Berry²

2013

Therapeutic Drug Monitoring

170

126

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“…TDM of newer AEDs in saliva has not yet been widely applied [5], but has been studied for six drugs: gabapentin [6], lamotrigine [7], levetiracetam [8], oxcarbazepine (main metabolite 10-hydroxycarbazepine) [9], topiramate [10] and zonisamide [11]. Of these six drugs, gabapentin appears to be clearly unsuited for salivary concentration analysis due to the low concentration in saliva versus plasma (salivary concentrations are ~5–10% that of serum or plasma).…”

Section: Background On Therapeutic Drug Monitoring Of Antiepileptimentioning

confidence: 99%

“…Zonisamide is rapidly absorbed after oral administration and is only 40–60% bound to serum proteins. Zonisamide distributes into saliva, but there is only limited data published on the relation between salivary and serum zonisamide concentrations [11]. Zonisamide displays linear pharmacokinetics but is extensively metabolized by oxidation, acetylation, and other pathways [180].…”

Section: Zonisamidementioning

confidence: 99%

Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

Krasowski

2010

Pharmaceuticals

103

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Abstract:In the past twenty years, 14 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. In general, the clinical utility of therapeutic drug monitoring has not been established in clinical trials for these new anticonvulsants, and clear guidelines for drug monitoring have yet to be defined. The antiepileptic drugs with the strongest justifications for drug monitoring are lamotrigine, oxcarbazepine, stiripentol, and zonisamide. Stiripentol and tiagabine are strongly protein bound and are candidates for free drug monitoring. Therapeutic drug monitoring has lower utility for gabapentin, pregabalin, and vigabatrin. Measurement of salivary drug concentrations has potential utility for therapeutic drug monitoring of lamotrigine, levetiracetam, and topiramate. Therapeutic drug monitoring of the new antiepileptic drugs will be discussed in managing patients with epilepsy.

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“…[11][12][13][14][15][16][17][18][19][20] Researchers also have considered lamotrigine, zonisamide, and oxcarbazepine for salivary therapeutic drug monitoring. [21][22][23][24][25] For lamotrigine specifically, two studies have examined the correlations between serum and saliva in adults. 23,25 However, neither study included individuals younger than 16 years.…”

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confidence: 99%