健康中国志愿者中头孢丙烯混悬剂和颗粒剂的药代动力学和生物等效性：两项单剂量交叉研究。

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

机构信息

Clinical Trial Center, The Affiliated Hospital of Qingdao University, Qingdao, China.

School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW, Australia.

出版信息

Adv Ther. 2021 Feb;38(2):1130-1142. doi: 10.1007/s12325-020-01593-7. Epub 2020 Dec 19.

DOI:10.1007/s12325-020-01593-7

PMID:33340343

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 C was (3534.70 ± 634.67) ng/ml, T was (0.98 ± 0.25) h, t was (1.37 ± 0.13) h and AUC was (9302.86 ± 1618.39) ng·h/ml, respectively, after a single dose of 125 mg cefprozil for suspension. Under fed conditions, the mean C was (2438.80 ± 493.78) ng/ml, T was (1.66 ± 0.76) h, t was (1.36 ± 0.24) h and AUC 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 C AUC and AUC 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.

摘要

简介

头孢丙烯，一种口服第二代半合成头孢菌素，具有广谱抗菌活性。已开发出颗粒制剂以提高患者的用药依从性。本研究旨在评估健康中国志愿者中颗粒制剂与干混悬剂的生物等效性，并估算头孢丙烯的药代动力学（PK）特征。

方法

在 60 名健康中国志愿者中进行了一项开放标签、随机、单剂量、两周期、两制剂、交叉研究，以评估两种头孢丙烯制剂之间的生物等效性。在禁食或进食条件下（每组 30 名志愿者）采集指定时间间隔的血样，并采用经验证的液相色谱-串联质谱（LC-MS/MS）法测定顺式和反式头孢丙烯的血浆浓度。采用非房室法估算 PK 参数和生物利用度。还记录了不良事件（AE）。

结果

在禁食条件下，单次口服 125mg 头孢丙烯混悬剂后，顺式和反式头孢丙烯的 C 分别为（3534.70±634.67）ng/ml、T 分别为（0.98±0.25）h、t 分别为（1.37±0.13）h 和 AUC 分别为（9302.86±1618.39）ng·h/ml。在进食条件下，C 分别为（2438.80±493.78）ng/ml、T 分别为（1.66±0.76）h、t 分别为（1.36±0.24）h 和 AUC 分别为（9332.36±1373.61）ng·h/ml。头孢丙烯颗粒制剂的 PK 参数与混悬剂相似。在禁食和进食条件下，C AUC 和 AUC 的 GMR 值的 90%CI 值均在预设的生物等效性范围内（80.00-125.00%）。