Objective: To study the pharmacokinetics of injected cefozopran hydrochloride in healthy volunteers.
Methods: 24 healthy volunteers were enrolled to receive low (0.5 g), middle (1.0 g), high (2.0 g) doses of single injection and multiple doses (1.0 g) injection of cefozopran hydrochloride in an open randomized study. The plasma concentrations of cefozopran were determined by RP-HPLC. The DAS2.0 was used to fit the concentration-time data and to calculate the pharmacokinetic parameters.
Results: The main pharmaeokinetic parameters for a single injection of low, middle and high doses of cefozopran were as follows: Cmax (48.27 +/- 9.84), (77.99 +/- 15.08) and (171.59 +/- 18.27) mg/L; Tmax (0.50 +/- 0.00), (0.51 +/- 0.02) and (0.51 + 0.02) h; AUCo-t (92.43 +/- 24.02), (152.45 +/- 16.26) and (341.03 +/- 44.16) mg x h/L; t1/2beta (1.97 +/- 0.19), (2.44 +/- 0.24) and (2.18 +/- 0.31) h, respectively. The main pharmacokinetic parameters for a multiple doses injection of cefozopran were as follows: Cmax (80.39 +/- 11.86) mg/L; Tmax (0.51 +/- 0.02) h; AUCo-t (159.74 +/- 15.06) mg x h/L; t1/2beta (2.55 +/- 0.55) h. The accumulative rate of cefozopran through urine pathway within 24 h was (89.4 +/- 15.5)%. The statistical analysis showed that Cmax, AUCo-t, and AUCo-infinity increased significantly with increased doses of injection (P < 0.05). Those parameters were linearly correlated with the doses of injection (r = 0.9950, 0.9960, 0.9963). However, dosage did not have an impact on other pharmacokinetic parameters (P > 0.05). No gender differences in the parameters were found (P > 0.05).
Conclusion: Cefozopran hydrochloride performs a linear kinetics in healthy volunteers. The main pharmacokinetic parameters have no significant gender differences, and there is no drug accumulated with multiple doses of injection.