MacCannell, D;
Berger, Z;
East, L;
Mercuri, E;
Kirschner, J;
Muntoni, F;
Farrar, MA;
... Finkel, RS; + view all
(2021)
Population pharmacokinetics-based recommendations for a single delayed or missed dose of nusinersen.
Neuromuscular Disorders
, 31
(4)
pp. 310-318.
10.1016/j.nmd.2021.02.014.
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Abstract
Nusinersen is an antisense oligonucleotide approved for the treatment of spinal muscular atrophy. The drug is given intrathecally at 12 mg, beginning with 3 loading doses at 2-week intervals, a fourth loading dose 30 days thereafter, and maintenance doses at 4-month intervals. This population pharmacokinetic model was developed to clarify how to maintain targeted nusinersen exposure after an unforeseen one-time delay or missed dose. Simulations demonstrated that the impact of a one-time delay in dosing or a missed dose on median cerebrospinal fluid exposures depended on duration of interruption and the regimen phase in which it occurred. Delays in loading doses delayed reaching the peak trough concentration by approximately the duration of the interruption. Resumption of the regimen as soon as possible resulted in achieving steady state trough concentration upon completion of the loading phase. A short delay (30-90 days) during the maintenance phase led to prolonged lower median cerebrospinal fluid concentration if all subsequent doses were shifted by the same 4-month interval. However, administration of the delayed dose, followed by the subsequent dose as originally scheduled, rapidly restored trough concentration. If a dose must be delayed, patients should return to the original dosing schedule as soon as possible.
| Type: | Article |
|---|---|
| Title: | Population pharmacokinetics-based recommendations for a single delayed or missed dose of nusinersen |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.nmd.2021.02.014 |
| Publisher version: | http://dx.doi.org/10.1016/j.nmd.2021.02.014 |
| Language: | English |
| Additional information: | © 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
| Keywords: | Delayed treatment, Dosing, Nusinersen, Pharmacokinetics, Spinal muscular atrophy |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10126154 |
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