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Armodafinil and Modafinil in Patients With Excessive Sleepiness Associated With Shift Work Disorder: A Pharmacokinetic/Pharmacodynamic Model for Predicting and Comparing Their Concentration‐Effect Relationships
Author(s) -
Darwish Mona,
Bond Mary,
Ezzet Farkad
Publication year - 2012
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270011417825
Subject(s) - modafinil , pharmacokinetics , pharmacodynamics , narcolepsy , pharmacology , placebo , medicine , anesthesia , multiple sleep latency test , polysomnography , wakefulness , methylphenidate , excessive daytime sleepiness , sleep disorder , psychiatry , attention deficit hyperactivity disorder , insomnia , pathology , electroencephalography , alternative medicine , apnea
Armodafinil, the longer lasting R‐isomer of racemic modafinil, improves wakefulness in patients with excessive sleepiness associated with shift work disorder (SWD). Pharmacokinetic studies suggest that armodafinil achieves higher plasma concentrations than modafinil late in a dose interval following equal oral doses. Pooled Multiple Sleep Latency Test (MSLT) data from 2 randomized, double‐blind, placebo‐controlled trials in 463 patients with SWD, 1 with armodafinil 150 mg/d and 1 with modafinil 200 mg/d (both administered around 2200 h before night shifts), were used to build a pharmacokinetic/pharmacodynamic model. Predicted plasma drug concentrations were obtained by developing and applying a population pharmacokinetic model using nonlinear mixed‐effects modeling. Armodafinil 200 mg produced a plasma concentration above the EC 50 (4.6 μg/mL) for 9 hours, whereas modafinil 200 mg did not exceed the EC 50 . Consequently, armodafinil produced greater increases in predicted placebo‐subtracted MSLT times of 0.5–1 minute (up to 10 hours after dosing) compared with modafinil. On a milligram‐to‐milligram basis, armodafinil 200 mg consistently increased wakefulness more than modafinil 200 mg, including times late in the 8‐hour shift.