Pharmacokinetics and safety of the two oral cefaclor formulations in healthy chinese subjects in the fasting and postprandial states

Abstract

We conducted a phase I bioequivalence trial in healthy Chinese subjects in the fasting and postprandial states. The goal of this trial was to compare the pharmacokinetics and safety of the test preparation Cefaclor granule (Disha Pharmaceutical Group Co., Ltd.) and the reference preparation Cefaclor suspension (Ceclor®, Eli Lilly and Company). In this trial, 24 subjects were selected in the fasting and postprandial states, respectively. Enrolled subjects randomly accepted a single dose of 0.125 g Cefaclor granule or Cefaclor suspension. The washout period was set as 2 days. Blood samples were collected within 8 h after administration in the fasting state and within 10 h after administration in the postprandial state. Plasma concentrations were determined by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters (AUC, Cmax) were used to evaluate bioequivalence of the two drugs. In the fasting trial, the geometric mean ratios (90% confidence intervals CIs) for Cmax, AUC0-t, and AUC0-∞ were 93.01% (85.96%–100.63%), 97.92% (96.49%–99.38%) and 97.95% (96.52%–99.41%), respectively. The GMR (90% CIs) for Cmax, AUC0-t, and AUC0-∞ in postprandial state were 89.27% (81.97%–97.22%), 97.31% (95.98%–98.65%) and 97.31% (95.93%–98.71%), respectively. The 90% CIs of AUC and Cmax in the fasting and postprandial states were within the 80–125% bioequivalence range. Therefore, Cefaclor granule and Cefaclor suspension were bioequivalent and displayed similar safety profiles. Furthermore, food intake affected the pharmacokinetic parameters of both drugs.

Quantification of cefaclor in human plasma using SIL‐IS LC‐ESI‐MS/MS for pharmacokinetics study in healthy Chinese volunteers

“…This study demonstrated a sensitive, rapid, and stable detection method with low plasma consumption. The pharmacokinetics study of healthy Chinese volunteers was carried out successfully using this method, and the pharmacokinetic parameters of cefaclor dry suspension were consistent with a previous report (Qu et al, 2022).…”

“…SIL-IS was seldom used in previous assays of cefaclor quantification in human plasma (Chen et al, 2003(Chen et al, , 2012Huang, Cadwallader, & Heltsley, 2014;Jiang et al, 2009;Kai et al, 2003;Koytchev et al, 2004;Li et al, 2010;Lindgren, 1987;Naz et al, 2017;Qu et al, 2022;Tutunji et al, 2001). As an ideal method for precise quantification using LC-ESI-MS/MS (Huang, Cadwallader, & Heltsley, 2014), SIL-IS has almost similar physical and chemical properties, retention times, and ionization to the analyte (Liu et al, 2019;Loos et al, 2016).…”

Pharmacokinetics of Antibacterial Agents in the Elderly: The Body of Evidence

“…Should not be taken with food to allow optimal absorption [110] Amoxicillin Cmax decreased, Tmax prolonged under fed condition, but with no change of the AUC, thus use both under fasted and fed state is effective, since it is time-dependent AB [111] Amoxicillin-clavulanate Decreased bioavailability of clavulanic acid after meal (extended-release tablets), so administration before meal is preferrable [112] Flucloxacillin Reduced AUC, Cmax, and prolonged Tmax of both free and total concentrations compared with the fasting state. Achievement of free concentration targets associated with efficacy was in most circumstances equivalent, suggesting no negative association with the fed state [113] Cefaclor Cmax decreased, Tmax delayed, but no AUC changes were reported for cefaclor granule and cefaclor suspension under fed state supposing effective use regardless of meal [114] Cefuroxime axetil Positive food effect on absorption with AUC in fed state greater than in the fasted state, suggesting postprandial administration be more effective [109] Cefpodoxime proxetil Achievement of proper Cmax and MIC values was reported in non-fasting patients. In the elderly patients, the absorption is approximately 30% lower compared to younger patients [115][116][117] Azithromycin Capsules have delayed disintegration under fed state, resulting in the extended gastric residence and gastric degradation of azithromycin, thus capsules should be taken only in the fasted state.…”