Tolerability, Safety, Pharmacokinetics and Drug Interaction of Cefotaxime Sodium–Tazobactam Sodium Injection (6:1) Following Single and Multiple Intravenous Doses in Chinese Healthy Subjects

Abstract

Purpose To evaluate the tolerability, safety, pharmacokinetics and drug interaction of cefotaxime sodium–tazobactam sodium injection (6:1) in Chinese healthy subjects. The results of the safety and pharmacokinetic studies supported further clinical trials. Method A randomized, single-blind, ascending dose, placebo-controlled, single-center study was conducted. Sixty healthy subjects (38 males, 22 females) participated in this study. For the single-dose part, 0.47, 1.17, 2.34, 3.51, and 4.68 g of cefotaxime sodium–tazobactam sodium injection (6:1) was administered. For the multiple-dose part, the subjects were administered 2.34 and 3.51 g cefotaxime sodium–tazobactam sodium injection (6:1) three times a day for 7 consecutive days. For the drug interaction part, the subjects received 2.0 g cefotaxime sodium and 0.34 g tazobactam sodium alone and in combination. Results Most adverse events and adverse drug reactions were mild. Moderate rash was considered a serious adverse event because of prolongation of hospitalization. The main pharmacokinetic parameters of cefotaxime and tazobactam had no significance difference between the 1.17, 2.34, and 3.51 g dose cohorts and between genders. There was no difference in trough concentrations on days 6, 7, and 8. The R C max and R AUC were (0.921 ± 0.070) and (0.877 ± 0.057) for cefotaxime, and (0.913 ± 0.046) and (0.853 ± 0.060) for tazobactam, respectively. Following the administration of cefotaxime and tazobactam alone and in combination, the 90% confidence intervals of the geometric mean ratios for C max and AUC were within the predetermined range of 80–125%. In the single-dose part, the renal cumulative excretion ratios were (51.7 ± 6.2)% for cefotaxime, and (84.3 ± 8.1)% for tazobactam. There was no significant difference in the maximum excretion rates and cumulative excretion ratios for cefotaxime and tazobactam, alone or in combination. Conclusions Cefotaxime sodium–tazobactam sodium injection (6:1) was well-tolerated at doses of 0.47 to 4.68 g. The pharmacokinetics of cefotaxime and tazobactam were reported as linear over a dose range of 1.17–3.51 g. Cefotaxime was partially excreted via urine, whereas tazobactam was mainly excreted via urine. There was no significant accumulation after administration over 7 consecutive days. The pharmacokinetics and excretion of cefotaxime and tazobactam were not affected by the co-administration of cefotaxime–tazobactam.

Efficacy of Etimicin Sulfate Combined with Cefotaxime Sodium in the Treatment of Patients with Septic Shock and Effect on Serum Inflammatory Factor Levels and Immune Function

“…It is widely used in the clinical treatment of pneumonia, urinary tract infection, and infectious diseases due to its advantages of broad antibacterial spectrum, strong antibacterial activity, less cross resistance, light adverse reaction, and high safety [ 6 ]. Cefotaxime sodium is the third generation of cephalosporin antibiotics which has the structure of β -lactam ring like penicillin, with a wide antibacterial spectrum and strong bactericidal effect [ 7 – 9 ]. Restricting the synthesis of cell wall mucopeptide synthase and inhibiting the synthesis of bacterial cell wall, in turn causes the bacterial body to swell and lyse to death is its antibacterial mechanism [ 10 , 11 ].…”