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Pharmacokinetics and Bioequivalence of Cefprozil for Suspension and Granule Formulation in Healthy Chinese Volunteers: Two Single-Dose Crossover Studies

Abstract

Introduction

Cefprozil, an oral second-generation semi-synthetic cephalosporin, possesses a broad spectrum of antimicrobial activity. A granule formulation has been developed to improve medication adherence of the patients. This study was conducted to assess the bioequivalence of the granule formulation to a dry suspension in healthy Chinese volunteers and estimate the pharmacokinetic (PK) profiles of cefprozil.

Methods

An open-label, randomized, single-dose, two-period, two-group, crossover study was conducted in 60 healthy Chinese volunteers under fasted or fed conditions (30 volunteers for each condition) to assess the bioequivalence between two formulations of cefprozil. Blood samples were collected at specified time intervals, and the plasma concentrations of cis- and trans-cefprozil were determined by a validated liquid chromatography-tandem mass spectrometry (LC–MS/MS) method. PK and bioavailability parameters were estimated via non-compartmental methods. Adverse events (AEs) were also recorded.

Results

Under fasted conditions, the mean Cmax was (3534.70 ± 634.67) ng/ml, Tmax was (0.98 ± 0.25) h, t1/2 was (1.37 ± 0.13) h and AUC0-t was (9302.86 ± 1618.39) ng·h/ml, respectively, after a single dose of 125 mg cefprozil for suspension. Under fed conditions, the mean Cmax was (2438.80 ± 493.78) ng/ml, Tmax was (1.66 ± 0.76) h, t1/2 was (1.36 ± 0.24) h and AUC0-t was (9332.36 ± 1373.61) ng·h/ml, respectively. The PK parameters of the granule formulation of cefprozil were similar to those of the suspension. The 90% CI values of the GMRs of Cmax, AUC0-t and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence range (80.00–125.00%).

Conclusions

According to the criteria for bioequivalence, the test granule formulations of cefprozil and "Cefprozil for Suspension®" were determined to be bioequivalent whether under fasted or fed conditions by measurement of cis-, trans- and total cefprozil.

Trial registration

ClinicalTrials.gov identifier, NCT04414254.

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Acknowledgements

The authors acknowledge the staff at Qilu Pharmaceutical Co., Ltd. (Jinan, China), for the administration of the study protocol and data collection. We thank the staff at Value Pharmaceutical Services Co., Ltd. (Nanjing, China), for the sample assay and PK analysis. We also acknowledge the staff at Guangzhou Jeeyor Medical Research Co., Ltd. (Guangzhou, China), for their support of the statistical analysis. We are grateful to the volunteers who participated in this study.

Funding

This study was funded by Qilu Pharmaceutical Co., Ltd., and by grants from the National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2020ZX09201-018). The Rapid Service Fee was supported by a research grant from the Affiliated Hospital of Qingdao University. The authors retained full control of the content of the manuscript. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of data analysis.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole and have given their approval for this version to be published.

Disclosures

Ping-Ping Lin, Chen-Jing Wang, Yan-Ping Liu, Ting Li, Xiao-Meng Gao, Ya-Ping Ma, Ping Shi, Xin Li, Le-Xin Wang and Yu Cao declare no conflict of interest.

Compliance with Ethics Guidelines

This clinical study protocol was approved by the Medical Ethics Committee at the Affiliated Hospital of Qingdao University. All procedures were performed in compliance with the Declaration of Helsinki as well as the International Conference on Harmonization Guideline for Good Clinical Practice. Informed consent was obtained from all volunteers prior to enrollment in the study.

Data Availability

The datasets generated and analyzed during the current study are available in the figshare repository, https://doi.org/10.6084/m9.figshare.13103342.

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Correspondence to Le-Xin Wang or Yu Cao.

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Lin, PP., Wang, CJ., Liu, YP. et al. Pharmacokinetics and Bioequivalence of Cefprozil for Suspension and Granule Formulation in Healthy Chinese Volunteers: Two Single-Dose Crossover Studies. Adv Ther 38, 1130–1142 (2021). https://doi.org/10.1007/s12325-020-01593-7

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Keywords

  • Bioequivalence
  • Cefprozil
  • Chinese
  • Healthy subjects
  • Infectious disease
  • Pharmacokinetics