Abstract
BACKGROUND AND OBJECTIVE: Tebipenem pivoxil (TP) is a carbapenem and is applied against pneumonia, otitis media, and sinusitis. This study compared the pharmacokinetics (PK) and safety of a test (T) preparation and reference (R) preparation of TP in healthy Chinese adults. METHODS: This study was a single-center, randomized, open, single-dose (fasting/postprandial) oral administration, two-agent, two-sequence, two-cycle, crossover bioequivalence trial. A total of 60 participants were enrolled (24 fasting and 36 postprandial). All participants were randomly assigned to the TR sequence and RT sequence. Subsequently, they switched T sequences or R sequences 7 days later. PK blood samples were collected according to the protocol, plasma TP concentration was determined by liquid chromatography-mass spectrometry, main PK parameters were calculated based on a non-compartment model, and adverse events were recorded during the test. RESULTS: In the feeding arm, the geometric mean ratio of maximum concentration (C(max)) was 89.84% (90% confidence interval 84.33-95.70), the geometric mean ratio of area under the plasma concentration-time curve from time 0 to last time of quantifiable concentration (AUC(0-t)) was 86.80% (83.62-90.10), and the geometric mean ratio of area under the plasma concentration-time curve from time 0 to infinity time of quantifiable concentration (AUC(0-∞)) was 86.90% (83.73-90.20), which were within the acceptable range of bioequivalence (80-125%). In the fasting arm, the geometric mean ratio of C(max) was 96.07% (89.62-102.99), the geometric mean ratio of AUC(0-t) was 93.09% (90.47-95.78), and the geometric mean ratio of AUC(0-∞) was 93.09% (90.48-95.77), which was within the acceptable range of bioequivalence (80-125%). Hence, the T preparation and R preparation of TP had bioequivalence in the fasting arm and feeding arm of the clinical trial. In addition, all adverse events were mild, and no severe adverse events were noted. CONCLUSION: Preparations T and R of TP were bioequivalent in the fasting and postprandial groups in clinical trials, and TP was safe.