Factors influencing topiramate clearance in adult patients with epilepsy: A population pharmacokinetic analysis

Bae, Eun‐Ah; Shin, Jai Moo; Moon, Jangsup; Lee, Keon‐Joo; Shin, Yong-Won; Kim, Tae‐Joon; Shin, Dong Wan; Jang, In‐Jin; Lee, Sang Kun

doi:10.1016/j.seizure.2016.02.002

Cited by 20 publications

(52 citation statements)

References 24 publications

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“…For the CL/F, this value was moderately higher, but is comparable with the findings of previous studies. 10,19,20 For the Vd/F, this value is partly consistent with some previous studies, 12 but is higher compared to other studies. 3,21 The PK parameters of topiramate previously reported are summarized in Table 4.…”

Section: Discussionsupporting

confidence: 92%

“…1,8 A pharmacokinetic linearity is reported over the dose range of 100 -800 mg. 4,8,9 To date, several population pharmacokinetic (PPK) analyses of topiramate have reported some significant covariates of topiramate apparent clearance (CL/F), such as age, body weight, renal function, and concomitant AEDs. [10][11][12] However, previous PPK studies have been performed primarily on only pediatric or adult populations.…”

Section: Discussionmentioning

confidence: 99%

“…Approximately half of topiramate in the body is excreted unaltered by the kidneys, 7,21 and eGFR was reported to be a significant covariate for the CL/F of topiramate. 4,12,22,23 In the present study, since only five patients with a moderate-to-severe renal impairment (eGFR of 55-60 mL/min/1.73 m 2 ) were included in the model-building data, we could not evaluate the effect of renal function on the topiramate CL/F. We also examined the effects of age especially for young children (2 to 6 years) and elderly people (60 years or more) on the CL/F in the final model.…”

Section: Discussionmentioning

confidence: 99%

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Population Pharmacokinetics of Topiramate in Japanese Pediatric and Adult Patients With Epilepsy Using Routinely Monitored Data

Takeuchi

Yano

Ito

et al. 2017

Therapeutic Drug Monitoring

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Population Pharmacokinetics of Topiramate in Japanese Pediatric and Adult Patients With Epilepsy Using Routinely Monitored Data

Takeuchi

Yano

Ito

et al. 2017

Therapeutic Drug Monitoring

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“…TPM clearance increased with the combined use of PHT, CBZ, OXC and PHB. The increase was up to 2.52 L/h after PHT, 2.17 L/h after CBZ, 1.803 L/h after OXC and 1.636 L/h after co-administration of PHB and was 117, 87, 55 and 41% higher, respectively, than in patients treated with TPM without concomitant treatment [175].…”

Section: Topiramatementioning

confidence: 81%

“…The TPM biological half-life becomes up to 50% shorter after administration with enzyme-inducing AEDs. Over 200 drugs are known to interact with TPM [100,175]. TPM clearance is also decreased by lithium, propranolol, amitryptiline and sumatriptan, diltiazem, hydrochlorthiazide, metformin, propranolol and, finally, posaconazole, increasing the level of TPM in serum [98].…”

Section: Topiramatementioning

confidence: 99%

Pharmacokinetic Drug–Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients

Karaźniewicz−Łada

Główka

Mikulska

et al. 2021

IJMS

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Anti-epileptic drugs (AEDs) are an important group of drugs of several generations, ranging from the oldest phenobarbital (1912) to the most recent cenobamate (2019). Cannabidiol (CBD) is increasingly used to treat epilepsy. The outbreak of the SARS-CoV-2 pandemic in 2019 created new challenges in the effective treatment of epilepsy in COVID-19 patients. The purpose of this review is to present data from the last few years on drug–drug interactions among of AEDs, as well as AEDs with other drugs, nutrients and food. Literature data was collected mainly in PubMed, as well as google base. The most important pharmacokinetic parameters of the chosen 29 AEDs, mechanism of action and clinical application, as well as their biotransformation, are presented. We pay a special attention to the new potential interactions of the applied first-generation AEDs (carbamazepine, oxcarbazepine, phenytoin, phenobarbital and primidone), on decreased concentration of some medications (atazanavir and remdesivir), or their compositions (darunavir/cobicistat and lopinavir/ritonavir) used in the treatment of COVID-19 patients. CBD interactions with AEDs are clearly defined. In addition, nutrients, as well as diet, cause changes in pharmacokinetics of some AEDs. The understanding of the pharmacokinetic interactions of the AEDs seems to be important in effective management of epilepsy.

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Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling

Lee,

Kim,

Jang

et al. 2023

Ann Clin Transl Neurol

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ObjectiveDespite the suggested topiramate serum level of 5–20 mg/L, numerous institutions have observed substantial drug response at lower levels. We aim to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range.MethodsWe retrospectively analyzed clinical data collected between January 2017 and January 2022 at Seoul National University Hospital. Drug responses to topiramate were categorized as “insufficient” or “sufficient” by reduction in seizure frequency ≥ 50%. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal cutoff values.ResultsA total of 389 epilepsy patients were reviewed having a mean dose of 178.4 ± 117.9 mg/day and the serum level, 3.9 ± 2.8 mg/L. Only 5.6% samples exhibited insufficient response, with a mean serum level of 3.6 ± 2.5 mg/L while 94.4% demonstrated sufficient response, with a mean 4.0 ± 2.8 mg/L, having no statistical significance. Among the 69 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (p = 0.04), with an optimal cutoff value of 6.5 mg/L.InterpretationThis study proposed an optimal therapeutic concentration for topiramate based on patients' responsiveness to the drug and the incidence of adverse effects. We recommended serum levels below 6.5 mg/L to mitigate the risk of ataxia‐related side effects while dose elevation was found unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses.

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Factors influencing topiramate clearance in adult patients with epilepsy: A population pharmacokinetic analysis

Abstract: The apparent clearance of topiramate increased with co-medication of PHT, CBZ, OXC, and PB. This population PK model can be applied for optimizing topiramate dosage regimens in actual clinical practice.

Cited by 20 publications

References 24 publications

Population Pharmacokinetics of Topiramate in Japanese Pediatric and Adult Patients With Epilepsy Using Routinely Monitored Data

Population Pharmacokinetics of Topiramate in Japanese Pediatric and Adult Patients With Epilepsy Using Routinely Monitored Data

Pharmacokinetic Drug–Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients

Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling

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