According to EMA’s Guideline on the Investigation of Bioequivalence [8], dose proportionality is to be assessed based on the AUC t parameter. The results of this study showed that the 90 % confidence interval of the dose-normalized geometric mean ratio of AUC t was within the range of 80 to 125 %. Consequently, this result indicates that the two strength formulations of doxylamine hydrogen succinate [12.5 mg (Dormidina® 12.5 mg film-coated tablets) and 25 mg (Dormidina® 25 mg

film-coated tablets) exhibited linear pharmacokinetics and that 12.5 mg and 25 mg of doxylamine hydrogen succinate Smad inhibitor were dose proportional in healthy subjects. Likewise, the pharmacokinetics of doxylamine show relatively low intra-subject variability. Updated data on the pharmacokinetic profile of doxylamine in humans after an oral dose of doxylamine hydrogen succinate 25 mg in film-coated tablets have recently been published [6]. As expected, the pharmacokinetic parameters after an oral dose of doxylamine hydrogen succinate 25 mg obtained in the present study were comparable to the ones in the abovementioned study [6]. Likewise, the overall results of this study are in line with studies performed with oral doses of 25-mg doxylamine succinate

tablets [5, 9, 10] and with oral doses of 20-mg doxylamine see more succinate solution [11, 12]. Doxylamine hydrogen succinate is available as an over-the-counter agent and is indicated for the symptomatic treatment of occasional insomnia in adults of 18 years of age and over. Overall, the two formulations tested (12.5- and 25-mg film-coated tablets) in this study were generally safe

and well tolerated. It should be noted that most of the subjects reported Cell Cycle inhibitor somnolence mainly when administered the 25 mg strength. In fact, 50 % (6 out of 12) of the subjects presented somnolence when administered the 25-mg dose, but only 17 % (2 out of 12) with 12.5 mg. It is to be note that the two subjects who presented somnolence with the 12.5-mg strength Methane monooxygenase also reported somnolence with the 25-mg dose. Actually, in the case of doxylamine, somnolence has to be considered as a pharmacodynamic effect associated with clinical efficacy in the short-term management of insomnia. Although this study was not designed to study the dose-proportional effect of doxylamine on somnolence, this result may suggest it. In clinical practice, the usual adult dose as nighttime sleep aid is 25 mg once daily, taken 30 min before bedtime. In fact, in clinical practice, the preponderance of side effects associated with this dose is related to a carryover to the next day of the hypnotic effects [13, 14]. This may be experienced primarily as continued drowsiness, tiredness or grogginess, “hangover” effect, sluggishness or lethargy. Therefore, given that the two strength formulations (12.