Tolerability and Pharmacokinetics of Biapenem Following Single and Multiple Intravenous Administrations in Healthy Chinese Subjects: An Open-Label, Randomized, Single-Center Study

Abstract

This study was designed to evaluate the tolerability and pharmacokinetics of biapenem after single and multiple intravenous administrations in healthy Chinese subjects. Subjects were randomly allocated to receive a single 0.15, 0.3, or 0.6 g dose of biapenem. Subjects assigned to the 0.3 g single dose group continued into the multiple-dose phase. Blood samples were collected over 6 h and plasma biapenem concentrations were determined by a validated HPLC method. Tolerability was assessed by monitoring vital signs, laboratory parameters, physical examinations, electrocardiogram, and adverse events collected by non-directive questioning/spontaneous reporting. Pharmacokinetic parameters for biapenem after intravenous administration of a single dose of 0.15, 0.3, or 0.6 g were as follows: C_max=7.06 (1.30), 15.59 (1.33), and 29.12 (1.22) mg/L; AUC_0–6 h=8.95 (1.33), 22.62 (1.25), and 42.05 (1.19) mg · h/L; t_1/2=0.97 (0.13), 1.04 (0.08), and 1.12 (0.08) h; CL=15.78 (1.32), 12.91 (1.24), and 13.95 (1.19) L/h; V_d=21.87 (1.25), 19.31 (1.25), and 22.41 (1.23) L, respectively. Pharmacokinetic parameters for biapenem after intravenous administration of multiple 0.3 g doses were as follows: C_max=18.50 (1.16) mg/L; AUC_0–6 h=26.45 (1.15) mg · h/L; t_1/2=1.06 (0.15) h; CL=11.06 (1.16) L/h; V_d=16.78 (1.19) L. The incidence of reported AEs was as follows: phlebitis (2/10), nausea (1/10), and diarrhea (1/10). All of the AEs were mild in intensity. The pharmacokinetic properties of biapenem were linear at dose of 0.15–0.6 g. All biapenem doses appeared to be well tolerated.

Key words

antibiotic - biapenem - pharmacokinetic study - safety - tolerability

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