Table I Summary of the main pharmacokinetic parameters of doxylamine Table II Standards for comparative bioavailability of doxylamine Fig. 1 Linear profile of the mean plasma concentrations of doxylamine in the fed and fasting selleck inhibitor states. Fig. 2 Logarithmic profile

of the mean plasma concentrations of doxylamine in the fed and fasting states. ln = log-normal. Table III Summary of the main pharmacokinetic parameters of doxylamine, analyzed by sex Tolerability and Safety No deaths or serious AEs were reported during this study. Twenty-one (87.5%) of the 24 subjects included in the study experienced a total of 54 AEs. Seventeen subjects (70.8%) reported 33 AEs (five different system organ classes [SOCs] and eight different preferred terms [PTs]) after single-dose administration of the test product under fed conditions, and 15 subjects (65.2%) reported 21 AEs (five different SOCs and six different PTs) after single-dose administration of the test product under fasting conditions. The most frequently reported AE was somnolence (reported in 70.8% of the subjects under fed conditions and in 56.5% of the subjects under fasting conditions). The severity of AEs ranged from mild to severe. Five severe AEs (four in the fed state: eczema, headache, somnolence [two occurrences];

one in the fasting state: somnolence) were observed during the study. Of all AEs, four (blood potassium level increased, feeling cold, and hypoesthesia [two occurrences]) were unexpected and possibly drug HDAC inhibitor related. No significant alterations were found in the

laboratory evaluations and the electrocardiogram repeated at the end of the study. Discussion To our knowledge, this selleckchem is the first time that the effect of food on the pharmacokinetic parameters of doxylamine has been studied. The results of this study show that the fed : fasting ratios of the geometric LS means and corresponding 90% confidence intervals for Cmax and AUCt were within the range of 80–125%. Consequently, the test formulation of doxylamine Staurosporine research buy hydrogen succinate 25 mg film-coated tablets manufactured by Laboratorios del Dr. Esteve SA (Barcelona, Spain) was judged to be bioequivalent under fed and fasting conditions. Data available on the pharmacokinetic profile of doxylamine in humans are limited, notwithstanding that this drug has been marketed in European countries for more than 50 years. In fact, the available studies on pharmacokinetic parameters after an oral dose of doxylamine succinate 25 mg were published more than 20 years ago.[6,8–10] It should be noted that this phase I clinical trial was one of the first to be performed in compliance with Good Clinical Practice and under the current regulatory standards. In the present study conducted under fasting and fed conditions, the pharmacokinetic parameters of doxylamine were not significantly affected by high-fat, high-calorie food intake. No statistically relevant differences in pharmacokinetic parameters between the two states were found.