dc.contributor.author | Kirkeby, Kjersti B | |
dc.contributor.author | Cockerell, Ine Tracey | |
dc.contributor.author | Christensen, Jakob | |
dc.contributor.author | Hoei-Hansen, Christina E. | |
dc.contributor.author | Holst, Lotte | |
dc.contributor.author | Fredriksen, Mikkel G | |
dc.contributor.author | Lund, Caroline | |
dc.contributor.author | Landmark, Cecilie Johannessen | |
dc.date.accessioned | 2024-08-12T07:06:34Z | |
dc.date.available | 2024-08-12T07:06:34Z | |
dc.date.created | 2024-08-11T12:20:56Z | |
dc.date.issued | 2024 | |
dc.identifier.issn | 0025-7974 | |
dc.identifier.uri | https://hdl.handle.net/11250/3145694 | |
dc.description.abstract | The mTOR-inhibitor everolimus is a precision drug with antiepileptogenic properties approved for treatment of epilepsy in persons
with tuberous sclerosis complex (TSC) in combination with other antiseizure medications (ASMs). However, the pharmacokinetic
variability of everolimus is scarcely described, and the available information on pharmacokinetic interactions is scarce. The
purpose of this study was to investigate pharmacokinetic variability of everolimus in patients with TSC, and the impact of age, sex
and comedication. In this retrospective observational study we used anonymized data from medical records of patients with TSC
using everolimus in Norway and Denmark, 2012 to 2020. Long-term therapeutic drug monitoring (TDM) identified inter-patient
and intra-patient variability. The study included 59 patients, (36 females (61%)), median age 22 (range 3–59 years). Polytherapy
was used in 50 patients (85%). The most frequently used ASMs were lamotrigine (n = 21), valproate (n = 17), and levetiracetam
(n = 13). Blood concentrations of everolimus were measured in all patients. Pharmacokinetic variability of everolimus between
patients was extensive, as demonstrated by a 24-fold variability from minimum–maximum concentration/dose (C/D)-ratios. The
coefficient of variation (CV) for intra-patient (n = 59) and inter-patient variability (n = 47, ≥3 measurements) was 40% and 43%,
respectively. The C/D-ratio of everolimus was 50% lower in 13 patients (22%) using enzyme-inducing ASMs compared to the 30
patients who did not (0.7 vs 1.4 ng/mL mg, P < .05). Age and sex were not significantly associated with changes in C/D-ratios
of everolimus. Long-term TDM identified extensive variability in concentrations over time for everolimus both within and between
patients, where comedication with enzyme-inducing ASMs was an important contributing factor. The findings suggest a need for
TDM in patients with TSC treated with everolimus. | en_US |
dc.language.iso | eng | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Pharmacokinetic variability of everolimus and impact of concomitant antiseizure medications in patients with tuberous sclerosis complex: A retrospective study of therapeutic drug monitoring data in Denmark and Norway | en_US |
dc.type | Peer reviewed | en_US |
dc.type | Journal article | en_US |
dc.description.version | publishedVersion | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.doi | 10.1097/MD.0000000000039244 | |
dc.identifier.cristin | 2285564 | |
dc.source.journal | Medicine | en_US |