Pharmacokinetics of Cefozopran by Single and Multiple Intravenous Infusions in Healthy Chinese Volunteers

BACKGROUND AND OBJECTIVES: Cefozopran is a parenteral cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative bacteria. The objective of this study was to evaluate the pharmacokinetics of cefozopran after single- and multiple-dose intravenous administration in healthy subjects, to provide clinical guidance in its application. METHODS: This was a single-center, open-label, randomized, two-phase study conducted in 12 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.5, 1.0 and 2.0 g of injected cefozopran hydrochloride in a three-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects received 2.0 g every 12 h for 4 days. Plasma and urine pharmacokinetic samples were assayed by a validated high-performance liquid chromatography–tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Safety assessments were conducted throughout the study. RESULTS: Twelve healthy volunteers (six males and six females) were enrolled and completed the study. Following a single 1-h intravenous infusion of 0.5, 1.0 or 2.0 g cefozopran, maximum plasma concentration (C (max)) and area under the plasma concentration–time curve from time zero to the time of the last measurable concentration (AUC(last)) increased in a dose-proportional manner. The mean half-life in plasma (t (½)) was in the range of 1.20–2.80 h. Cefozopran was mainly excreted in its unchanged form, with no tendency for accumulation, via the kidney, and varied from 65.99 to 73.33 %. No appreciable accumulation of either drug occurred with multiple intravenous doses of cefozopran, and pharmacokinetic parameters for cefozopran were similar on days 1 and 4. No serious adverse events were reported. Adverse events were generally mild. CONCLUSION: Cefozopran was safe and well tolerated in the volunteers and displayed linear increases in the C (max) and AUC(last) values.