Pharmacokinetics and Bioequivalence of 2 Immediate‐Release Tofacitinib Tablet Formulations in Chinese Healthy Volunteers Under Fasting and Fed Conditions

Abstract

The purpose of this study was to evaluate the bioequivalence of a generic immediate-release tofacitinib tablet versus a brand-named immediate-release tofacitinib tablet under fasting and fed conditions, and the food effect on pharmacokinetic profiles of the both formulations. This randomized, open-label, 2-period, crossover, bioequivalence study included 52 healthy Chinese subjects (fasting cohort: n = 26; fed cohort: n = 26). The subjects were assigned to receive a single 5-mg dose of generic or brand-named tofacitinib. Blood samples were collected at predosing and up to 14 hours after dosing. Tofacitinib concentrations in plasma were analyzed by high-performance liquid chromatography-tandem mass spectrometry. Safety was monitored. There were no significant differences in maximum plasma concentration, area under the plasma concentration-time curve from time zero to time t (AUC 0-t ), AUC from time zero to infinity (AUC 0-∞ ) , and terminal elimination half-life between the test and reference formulations (all P > .05); high-fat food had no significant effect on AUC 0-t , AUC 0-∞, or terminal elimination half-life of immediate-release tofacitinib tablets (all P > .05). The 90% confidence intervals of the test/reference ratios of log-transformed maximum plasma concentration, 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 2 formulations of immediate-release tofacitinib tablets are bioequivalent and well tolerated under both fasting and fed conditions in healthy Chinese volunteers. Food had no clinically relevant effects on drug exposure of tofacitinib.

Bioequivalence and Safety of Two Formulations of Tofacitinib Citrate Tablets in Healthy Chinese Volunteers under Fasting and Fed Conditions: Randomized, Open-Label, 2-Period, Single-Dose, Crossover Trials

“…However, another study showed that a high-diet had no efect on AUC 0-t and AUC 0-∞ [14]. In our study trial, the value of t 1/2 was in average delayed 0.45 h after a high-fat diet, and it is diferent to the previous studies [12,14]; the previous study showed that there was no signifcant difference in the value of t 1/2 . But in another study [13], it was also proven that a high-fat diet can extend t 1/2 about 0.2 h. Overall, a high-fat diet can afect the pharmacokinetic behavior of tofacitinib.…”

“…In our study trial, the values of C max and T max are similar to previous studies and food afection on exposure of tofacitinib. Te value of C max in average decreased by 25.90%, and it is similar to previous studies [12][13][14]. In our study, the value of AUC 0-t and AUC 0-∞ was in average increased by 16.57% and 14.08%, respectively, after a high-fat diet in the fasted state, which is similar to the previous study [13].…”

“…Previous studies demonstrated that the pharmacokinetic profle of tofacitinib is characterized by rapid absorption, T max are within 0.5-1.5 h, and t 1/2 are within 2-3.5 h [12,13]. In our study trial, the values of C max and T max are similar to previous studies and food afection on exposure of tofacitinib.…”

“…Te aim of this study was to evaluate the bioequivalence between a preparation of tofacitinib citrate tablets developed by Jiangxi Qingfeng Pharmaceutical Co. Ltd. and the reference preparation of tofacitinib citrate tablets (Xeljanz ® ) developed by Pfzer Manufacturing Deutschland Gmbh in healthy Chinese volunteers and observed the safety of both. (12) difculty in blood collection, patients who cannot tolerate venipuncture, and people with a history of needle sickness and blood sickness; (13) excessive intake of tea, cofee, or other caffeinated beverage; (14) intake of drinks or foods rich in cafeine or grapefruit or ingesting any beverage or food rich in cafeine or grapefruit within 48 hours before the frst administration of the study; (15) ingestion of drugs within 30 days before study drug administration; and (16) pregnancy or lactation.…”

Pharmacokinetics, Bioequivalence, and Safety of 2 Formulations of Hydroxychloroquine Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions

“…Suitable healthy Chinese subjects were included in our study. The inclusion criteria were as follows: (1) aged >18 years, both men and women; (2) male subjects weighing more than 50 kg and female subjects weighing more than 45 kg; body mass index 19–26 kg/m 2 , including the boundary value; (3) subjects provided informed consent before participating in the study; and (4) subjects were able to communicate well with the researcher and understand and comply with the requirements of the study 16,17 . The exclusion criteria are shown in Supplemental Information .…”