Use of computer simulations to test the concept of dose forgiveness in the era of extended-release (XR) drugs

Abstract “Forgiveness” – the difference between a drug's postdose duration of action and its prescribed dosing interval – estimates the margin of therapeutic effect following a missed dose. Because this margin presumably decreases as dosing becomes less frequent, QD dosing of an antiepileptic d...

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Bibliographic Details
Published in:Epilepsy & behavior 2016-02, Vol.55, p.21-23
Main Authors: Pellock, John M, Brittain, Scott T
Format: Article
Language:English
Subjects:
Adherence
Anticonvulsants - administration & dosage
Anticonvulsants - pharmacokinetics
Anticonvulsants - therapeutic use
Chemistry, Pharmaceutical
Computer Simulation
Dose-Response Relationship, Drug
Epilepsy - drug therapy
Extended-release
Forgiveness
Humans
Medication Adherence
Models, Theoretical
Neurology
Self-Sustained Sequence Replication
Simulation
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Summary:Abstract “Forgiveness” – the difference between a drug's postdose duration of action and its prescribed dosing interval – estimates the margin of therapeutic effect following a missed dose. Because this margin presumably decreases as dosing becomes less frequent, QD dosing of an antiepileptic drug (AED) is expected to be less forgiving than more frequent (e.g., BID) dosing of that same AED. However, if the AED is reformulated as an extended-release (XR) preparation, drug input may be prolonged relative to its immediate-release (IR) counterpart. It therefore stands to reason that forgiveness could be increased by an XR AED that extends the period during which therapeutic plasma concentrations are maintained if a dose is missed. Computer simulation was used to estimate forgiveness for an IR formulation of a hypothetical AED and its XR counterparts reformulated for less frequent dosing. Simulations determined forgiveness when the hypothetical IR AED was dosed TID, BID, and QD and when suitably designed XR formulations were dosed BID and QD. Simulations showed that forgiveness for an XR formulation can equal or exceed that for an IR formulation dosed more frequently.
ISSN:1525-5050
1525-5069
DOI:10.1016/j.yebeh.2015.11.029