Jing Shan, Wang Xin, Yang Kexu, Liu Wenfang, Li Jing, Tan Li, Suo Wei, Lu Chunyan, Lin Yang
Objective To evaluate the postprandial bioequivalence of domestic and original glucosamine sulfate capsules in Chinese healthy volunteers. Methods The trial was a single-center, randomized, open-label, single-dose, 2-preparation, 3-sequence, 3-period, partially repeated crossover design. The trialed drugs were domestic glucosamine sulfate capsules Yisuojia (test preparation) and original glucosamine sulfate capsules Viartril- (reference preparation). Healthy subjects were randomly divided into 3 groups, each group took medicine in 3 periods, but the order of taking test preparation (T) and reference preparation (R) was different, which were TRR, RTR and RRT groups. The healthy volunteers in the TRR, RTR, and RRT groups received the trialed drugs orally 30-minutes after diet supply on day 1, 4, and 7, respectively. Peripheral venous blood samples 4-ml were collected at 1-2 hours after dinner the day before medication (baseline 1), within 60-minutes before medication (baseline 2), and 15, 30, 45, 60, 90, 120, and 150-minutes and 3, 4, 5, 6, 8, 10, 14, and 16-hours after medication, respectively. Plasma was collected after centrifugation, frozen, and stored. Liquid chromatography-tandem mass spectrometry was used for the determination of glucosamine concentrations in plasma samples and main pharmacokinetic parameters such as the area under the concentration-time curve(AUC), including areas from time zero (pre-dose) to the last measurable concentration (AUC0-t) and extrapolated to infinite time (AUC0-∞), and peak concentration (Cmax) were calculated. Because glucosamine was an endogenous substance in humans, the measured blood concentration of glucosamine was corrected by subtracting the baseline value before medication (the average of baseline 1 and baseline 2). The test and reference preparations were equivalent when the geometric mean ratios (GMR) and their 90% confidence intervals (CI) for AUC0-t, AUC0-∞, and Cmax all ranged from 0.800 to 1.250. Results A total of 30-healthy volunteers were enrolled in the study, including 20 males and 10 females, aged (31±7) years with a range of 18-45 years. Ten volunteers were included in each TRR, RTR, and RRT group. One volunteer fell off in the TRR group after the first period of medication and the remaining 29 volunteers completed the trial. The baseline uncorrected GMR (90%CI) of AUC0-t, AUC0-∞, and Cmax for the test and the reference preparations were 0.985 (0.941-1.031), 1.014 (0.961-1.070), and 0.937 (0.827-1.062), respectively; the baseline corrected GMR (90%CI) of AUC0-t, AUC0-∞, and Cmax of the test and the reference preparations were 0.977 (0.923-1.035), 0.976 (0.922-1.032), and 0.932 (0.817-1.063), respectively, which all fell within the equivalence range (0.800-1.250). During the trial, no adverse events related to the trialed drugs occurred in the 3 groups. Conclusion Domestic glucosamine sulfate capsules were bioequivalent to the original when taken after diet and had a good safety profile.
