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 M, Bond M, Ezzet F.
Affiliation(s): Clinical Pharmacology Department, Cephalon, Inc., 41 Moores Road, Frazer, PA
19355, USA. firstname.lastname@example.org
Publication date & source: 2012, J Clin Pharmacol. , 52(9):1328-42
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.