Pharmacokinetics and Bioequivalence of Fudosteine in Healthy Chinese Volunteers Under Fasting and Fed Conditions: A 4‐Way Replicate Crossover Study

Abstract

The bioequivalence of a generic fudosteine tablet vs a brand-named fudosteine tablet under fasting and fed conditions was evaluated in this study. This randomized, open-label, single-dose, 4-way replicate, crossover, bioequivalence study included 64 healthy Chinese subjects (fasting cohort, n = 32; fed cohort, n = 32) who were assigned to receive a single 200-mg dose of generic or brand-named fudosteine. Blood samples were collected before dosing and up to 24 hours after dosing. The plasma concentrations of fudosteine were analyzed by high-performance liquid chromatography-tandem mass spectrometry. Safety was monitored. There were no significant differences in maximum plasma concentration (C max ), area under the plasma concentration-time curve (AUC) from time 0 to time t (AUC 0-t ), or AUC from time 0 to infinity (AUC 0-∞ ) between the test and reference formulations.However,food showed a significant effect on C max ,AUC 0-t , and AUC 0-∞ for both generic and brand-named fudosteine. The 90%CIs of the test/reference ratios of C max , AUC 0-t, and AUC 0-∞ were within the range of 80% to 125% under both fasting and fed conditions. No serious adverse events were reported. The bioequivalence between generic and brand-named fudosteine under fasting and fed conditions was demonstrated. Both of them had good tolerance for healthy Chinese volunteers. In addition, food delayed the absorption of fudosteine, so taking this medicine before meals might be an optimized option. Keywordsbioequivalence, fasting and fed, fudosteine, highly variable drug, pharmacokinetics Airway mucus hypersecretion plays an important role in patients with chronic airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, which affect an estimated 420 million individuals worldwide. 1 As a consequence, for patients, an augmented amount of secretion is associated with the principal symptoms, namely dyspnea, coughing, and the occurrence of respiratory complications. Thus, effective mucus clearance is essential for lung health. 2,3 Available treatments for promoting mucus clearance are as follows: physical measures, bronchodilators, inhaled dornase alfa, inhaled hypertonic saline, and N-acetylcysteine. 3 Fudosteine, (-)-(R)-2-amino-3-((3-hydroxypropyl) thio) propionic acid (SS320A) (Figure 1), is a cysteine derivative that was approved in Japan in 2001 as a mucoactive agent for the treatment of chronic respiratory diseases, such as bronchial asthma, chronic bronchitis, pulmonary emphysema, and so on. 4 The multiple pharmacological effects of fudosteine on