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  • Blanka Koristkova,
  • Milan Grundmann,
  • Ivana Kacirova,
  • Hana Brozmanova
Blanka Koristkova
University of Ostrava Faculty of Medicine
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Milan Grundmann
University of Ostrava Faculty of Medicine
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Ivana Kacirova
University of Ostrava Faculty of Medicine
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Hana Brozmanova
University of Ostrava Faculty of Medicine
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Aim: The Norwegian Association for Clinical Pharmacology in their National Guidelines decreased therapeutic range (TR) of topiramate (TPM) from 5-20 mg/L to 2-10 mg/L. The objective of this study is to ascertain which TR produces better clinical outcomes. Methods: Data source were request forms for routine therapeutic drug monitoring of TPM. Concentration dependent adverse drug reactions (ADRs) were evaluated in 1,721 samples taken pre-dose. Seizure frequency analysis was performed in 294 samples of monotherapy. Statistics: Prism 5.0, GraphPad Instatt: Mann–Whitney U test for median plasma level (PL). χ2-test for seizure frequency and for distribution of PL according to TR 5-20 mg/L and intervals <2, 2-5, 5-10, 10-20, >20 mg/L. Results: Better seizure control was found in children both in whole cohort (without seizure 49% vs 37% adults), as well as in monotherapy (56% vs 44%), in children with PL 5-20 mg/L vs 5 mg/L (65% vs 44%) and in children with PL 5-10 mg/L vs <2 mg/L. Seizure-free children had higher PL than those with seizure yearly: median (lower, upper quartile) [mg/L]: 5.5 (3.4-6.5) vs 4.7 (4.3-7.95). No difference was found in adults. Seizure control was poorer in all patients with PL <2 mg/L compared to 5-10 mg/L; and 10-20 mg/L; further in PL within 5-10 mg/L vs 10-20 mg/L; and in the period 2003-2005. ADRs reported in 38 samples (2.8%) were without relation to PL. Conclusions: Change of TR is not recommended.

Peer review status:IN REVISION

09 Mar 2021Submitted to British Journal of Clinical Pharmacology
10 Mar 2021Assigned to Editor
10 Mar 2021Submission Checks Completed
15 Mar 2021Reviewer(s) Assigned
20 May 2021Review(s) Completed, Editorial Evaluation Pending
22 May 2021Editorial Decision: Revise Major