The long half-life also is likely t

The long half-life also is likely to affect efficacy, particularly for sleep latency, which is moredependent than sleep maintenance on the time between dosing and blood levels reaching aneffective level. At the first dose, suvorexant blood level must go from zero to some levelbefore the drug could be effective. However, with chronic dosing of 40 mg, suvorexant bloodlevel at bedtime, before taking that night’s dose, is already about the same as Cmax from the10 mg dose, a dose seemingly effective for sleep latency. This same relationship holds for anydose (with the steady-state suvorexant level proportional to the dose), such that potentiallyeven if a low dose (10 mg or even lower) is less effective on night 1 for sleep latency than ahigh dose, on subsequent nights of chronic dosing, accumulation of suvorexant would allowsuvorexant blood levels to more quickly reach an effective level. The difference in efficacybetween low and high dose would diminish because, while the high dose would also lead toaccumulation of suvorexant, the exposure from the high dose would already have been in ornear the plateau region of the dose-response relationship, such that higher exposure wouldlead to little if any greater efficacy.