Fasting bioequivalence and safety assessment of domestic versus original pyrazinamide tablets
10.3760/cma.j.cn114015-20220316-00206
- VernacularTitle:国产与原研吡嗪酰胺片空腹状态下服用的生物等效性和安全性研究
- Author:
Wei SUO
1
;
Shan JING
1
;
Wenfang LIU
1
;
Chunyan LU
1
;
Kexu YANG
1
;
Jingyi LIU
1
;
Li TAN
1
;
Jing LI
1
;
Guiping ZHAO
1
;
Yang LIN
1
Author Information
1. 首都医科大学附属北京安贞医院药事部，北京 100029
- Publication Type:Journal Article
- Keywords:
Pyrazinamide;
Equivalence trial;
Pharmacokinetics;
Safety
- From:
Adverse Drug Reactions Journal
2022;24(6):295-299
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the bioequivalence and safety of domestic and original pyrazinamide tablets under fasting condition.Methods:A single center, randomized, open-label, two period self-crossover trial was conducted in healthy adult volunteers. The test preparation (T) of pyrazinamide tablets was produced by Taicang Pharmaceutical Factory and the reference preparation (R) was produced by A&Z Pharmaceutical Inc. (Pyrazinamide ?). The healthy subjects were randomly divided into 2 groups and took the drugs for 2 times with different order in each group, which were R-T group (subjects took R on day 1 and then T on day 8) and T-R group (subjects took T on day 1 and then R on day 8). Pharmacokinetic parameters were used as endpoints to assess the bioequivalence. Peripheral venous blood samples (3 ml) were collected from subjects within 1 hour before taking the drug and at 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, and 210 minutes and 4, 5, 6, 8, 12, 24, 36, and 48 hours after taking the drug. Plasma was frozen after centrifugation of the blood samples. The plasma pyrazinamide concentrations were determined by a tandem liquid chromatography-mass spectrometry method and the main pharmacokinetic parameters such as peak concentration ( Cmax) and the area under the concentration-time curve (AUC), including AUC from time zero (pre-dose) to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞), were calculated. The test and reference preparations were judged as bioequivalence when the 90% confidence intervals ( CI) of geometric mean ratios for AUC 0-t, AUC 0-∞, and Cmax all ranged from 0.80 to 1.25. Adverse events occurred in subjects during the trial were observed and recorded. Results:A total of 24 healthy volunteers were enrolled in the trial, including 16 males and 8 females aged 18-50 years, with 12 in the R-T and T-R groups, respectively. All subjects completed the trial. After taking medicine under fasting condition, the 90% CI of the geometric mean ratios of Cmax, AUC 0-t, and AUC 0-∞ for the test and reference preparations were 0.93-1.09, 0.98-1.03, and 0.98-1.03, respectively. During the trial, the incidence of adverse events was 25.0% (6/24) and 3 cases occurred after taking the test and reference preparations respectively, which were grade 1 in severity. Conclusion:The domestic and original pyrazinamide tablets were bioequivalence and with good safety when taken under fasting condition.
