Pharmacokinetics and Bioequivalence of 2 Safinamide Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions

Abstract

To assess the bioequivalence of a generic safinamide tablet (test) vs a brand-name safinamide tablet (reference) and effects of food on the pharmacokinetics of safinamide in healthy Chinese subjects,a single-center,single-dose,randomized, open-label, 2-preparation, 2-period study with a 15-day washout period was undertaken. A total of 56 healthy subjects were recruited in this study (fasting, n = 28; fed, n = 28). A single dose of a 100-mg test or reference safinamide tablet was administered to each subject in a randomized sequence. Blood samples were obtained at 5 minutes before drug administration and during the 120 hours after dosing. The safinamide concentration in plasma was determined by high-performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were analyzed with noncompartmental methods. Safety was also monitored. The major pharmacokinetic parameters including maximum plasma drug concentration, area under plasma concentration-time curve (AUC) from zero to time t (AUC 0-t ), and AUC from time 0 to infinity (AUC 0-∞ ) were similar between the test and reference tablets under fasting and fed conditions. The 90% CIs of the test/reference ratios of log-transformed maximum plasma drug concentration, AUC from zero to time t, and AUC from time 0 to infinity all fell within the equivalence interval (80.0%-125%) whether under fasting condition or fed condition. In conclusion, the 2 formulations of safinamide tablets were bioequivalent and well tolerated under both fasting and fed conditions in healthy Chinese volunteers. High-fat food delayed the absorption of safinamide but did not affect the final bioavailability.

Pharmacokinetic and Safety Study of Single and Multiple Oral Doses of Safinamide in Healthy Chinese Volunteers

“…Plasma safinamide concentrations and pharmacokinetic data of this study are in line with the results of published data in both Chinese and non-Asian populations. In the study by Li et al, 39 for the reference safinamide product, which corresponded to the investigational product of the present study and was administered as a single 100-mg dose under fasting conditions, mean C max value was 820.2 ng/mL, that is, very similar to the C max value for the same dose regimen obtained in the present study (792.1 ng/mL at day 1 and 825.3 ng/mL at day 8). In the two studies, C max was obtained at a median time of 1.5-1.8 h.…”

“…17 Age, sex, renal function, and exposure to L-dopa do not have an impact on the pharmacokinetics of safinamide. 38 A previous pharmacokinetic study conducted on healthy Chinese volunteers 39 who received safinamide as a 100-mg single dose of a test and a reference safinamide tablet established the bioequivalence of the 2 formulations in terms of both safinamide rate and extent of absorption under both fasting and fed conditions. In addition, as previously observed in non-Asian subjects, 28,30 high-fat food delayed the absorption of safinamide but did not affect its final bioavailability.…”