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Simulations of topiramate dosage recommendations for poor compliance events

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To determine the influences of one or two consecutive missed topiramate (TPM) doses on TPM pharmacokinetics and to suggest the proper TPM replacement dosing schemes using Monte Carlo simulations.

Methods

Monte Carlo simulations were performed for various replacement dosing schemes using the parameters from the published population pharmacokinetic models. The lowest percentage of deviation of simulated concentrations outside the reference range of 5–20 mg/L from the compliance scenario for each replacement dosing scheme was used as a criterion for choosing the proper replacement dosing scheme.

Results

For the one missed dose, the replacement with an immediate regular dose and a partial dose resulted in the lowest and highest percentages of concentration below 5 mg/L, respectively. While the opposite results were observed for the upper bound of the reference range (20 mg/L). For the two consecutive missed doses, the replacement with one and a half-missed doses resulted in a lower percentage of deviation of concentrations below 5 mg/L from the compliance scenario than the replacement with one regular dose.

Conclusions

For the one missed dose, taking an immediate regular dose might be suitable for patients who require higher TPM levels, while for patients who require lower TPM levels, an immediate partial dose could be used. For the two consecutive missed doses, an immediate one and a half regular dose might be suitable. However, these results were merely based on simulations; thus, they should be used alongside the clinician’s justification based on seizure control.

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Authors and Affiliations

  1. Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand

    Janthima Methaneethorn

  2. Center of Excellence for Environmental Health and Toxicology, Naresuan University, Phitsanulok, Thailand

    Janthima Methaneethorn

  3. Pharmaceutical Care Service, Department of Pharmacy, Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand

    Wanaporn Charoenchokthavee

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  1. Janthima Methaneethorn
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  2. Wanaporn Charoenchokthavee
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Contributions

JM planed, designed, and analyzed the study. JM drafted the initial manuscript. WC critically reviewed and provided constructive comments. Both authors approved the final version of the manuscript.

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Correspondence to Janthima Methaneethorn.

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Methaneethorn, J., Charoenchokthavee, W. Simulations of topiramate dosage recommendations for poor compliance events. Eur J Clin Pharmacol 78, 1843–1850 (2022). https://doi.org/10.1007/s00228-022-03390-3

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  • DOI: https://doi.org/10.1007/s00228-022-03390-3

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