Objective: The aim of the study was to investigate the different extent of inhibition of endogenous insulin secretion by the reduction of C-peptide levels in an euglycemic clamp study and its effects on the evaluation of pharmacokinetics, pharmacodynamics of insulin preparations, and quality of clamp study to determine the best reduction range of C-peptide levels.Methods: Healthy Chinese male volunteers were enrolled and underwent a single-dose euglycemic clamp test. Participants were subcutaneously injected with long-acting insulin glargine (0.4 IU/kg). Blood samples were collected pretest and up to 24 h post-test to assess pharmacokinetics (PK), pharmacodynamics (PD), and C-peptide levels.Results: We divided the 39 volunteers enrolled in the study into three groups according to the reduction of C-peptide levels: group A (ratio of C-peptide reduction <30%, n = 13), group B (ratio of C-peptide reduction between ≥ 30% and <50%, n = 15), and group C (ratio of C-peptide reduction ≥50%, n = 11); there were significant differences in the three groups (p= 0.000). The upper and lower limits of blood glucose oscillation in group C was statistically lower than the other groups, the range of oscillating glucose levels in group C was −17.0 ± 6.6% to −1.1 ± 6.7%. The AUC0–24 h in groups A, B, and C were 9.7 ± 2.2, 11.0 ± 2.9, and 11.9 ± 2.1 ng/ml × min, respectively, which indicated an increasing trend in the three groups (Ptrend = 0.041). For quality assessment, the average glucose (p = 0.000) and MEFTG (p = 0.001) levels in three groups were significantly different.Conclusion: The different extent of inhibition of endogenous insulin will influence the PK/PD of insulin preparations and the quality of the euglycemic clamp. Furthermore, the ratio of C-peptide reduction should be above 50% to free from the interference of endogenous insulin, and the range of blood glucose levels should be consistently maintained at −10% to 0 in the euglycemic clamp.

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

Aim To evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and bioequivalence of two insulin glargine preparations in Chinese healthy male subjects. Methods Randomized, open, two-sequence, four-period, single-dose, crossover design was applied in this study. A total of 40 healthy Chinese men were recruited and randomly divided into RTRT or TRTR groups. Pharmacodynamic parameters of the preparations were measured by a 24h euglycemic clamp test. Plasma insulin glargine concentration and C-peptide were collected during the trial and analyzed by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) and enzyme-linked immunosorbent assay (ELISA). SAS V9.4 was used for calculation of pharmacodynamic and pharmacokinetic parameters and the equivalence of the two preparations. Results The average concentration of C-peptide of each sequence was lower than the baseline. PK parameters cmax of the test and the reference preparation insulin glargine were 0.580 and 0.614 ng·mL− 1, and the AUC0 − 24hwere 9.782 and 10.436 h·ng·mL− 1, respectively. PD parameters GIRmax were 42.748 and 45.279 mg·kg− 1·min− 1, AUCGIR,0−24h were 2.924 and 3.096 h·mg·kg− 1·min− 1, respectively. There was no clinically significant adverse reaction observed during the experiment. Conclusion The quality of the glucose clamp in this study is superior. The test insulin Glargine was bioequivalent with the reference preparation.