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Drug Res (Stuttg) 2013; 63(08): 396-403
DOI: 10.1055/s-0033-1341498
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

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

Y. Liu
1   Clinical Research Organization for Pharmaceutical Products, Union ­Hospital, Tongji Medical College, Huazhong University of Science and ­Technology, Wuhan, People’s Republic of China
,
Z. Li
1   Clinical Research Organization for Pharmaceutical Products, Union ­Hospital, Tongji Medical College, Huazhong University of Science and ­Technology, Wuhan, People’s Republic of China
,
C. Yang
1   Clinical Research Organization for Pharmaceutical Products, Union ­Hospital, Tongji Medical College, Huazhong University of Science and ­Technology, Wuhan, People’s Republic of China
,
H. Zheng
2   Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, ­Wuhan, People’s Republic of China
,
Y. Lv
1   Clinical Research Organization for Pharmaceutical Products, Union ­Hospital, Tongji Medical College, Huazhong University of Science and ­Technology, Wuhan, People’s Republic of China
,
H. Chen
1   Clinical Research Organization for Pharmaceutical Products, Union ­Hospital, Tongji Medical College, Huazhong University of Science and ­Technology, Wuhan, People’s Republic of China
3   Institute of Clinical Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ­People’s Republic of China
,
Y. Zhang
1   Clinical Research Organization for Pharmaceutical Products, Union ­Hospital, Tongji Medical College, Huazhong University of Science and ­Technology, Wuhan, People’s Republic of China
,
S. Shi
1   Clinical Research Organization for Pharmaceutical Products, Union ­Hospital, Tongji Medical College, Huazhong University of Science and ­Technology, Wuhan, People’s Republic of China
› Author Affiliations
Further Information

Publication History

received 09 January 2013

accepted 11 March 2013

Publication Date:
12 April 2013 (online)

Also available at
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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: Cmax=7.06 (1.30), 15.59 (1.33), and 29.12 (1.22) mg/L; AUC0–6 h=8.95 (1.33), 22.62 (1.25), and 42.05 (1.19) mg · h/L; t1/2=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; Vd=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: Cmax=18.50 (1.16) mg/L; AUC0–6 h=26.45 (1.15) mg · h/L; t1/2=1.06 (0.15) h; CL=11.06 (1.16) L/h; Vd=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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