Vol.58 No.S-1 March 2010
Clinical pharmacological study of tazobactam/piperacillin in patients with community-acquired pneumonia
1)Research Division for Development of Anti-Infective Agents, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo, Aoba-ku, Sendai, Miyagi, Japan
2)Department of Internal Medicine, Shinrakuen Hospital
3)Department of Clinical Infectious Diseases, Showa University School of Medicine
4)Japanese Red Cross Nagasaki Genbaku Isahaya Hospital
5)Division of Molecular and Clinical Microbiology, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences (Second Department of Internal Medicine)
6)Jikei University School of Medicine
Abstract
A clinical pharmacological study of tazobactam/piperacillin(TAZ/PIPC), a β-lactamase inhibitor combined with penicillin antibiotic, was conducted on patients with community-acquired pneumonia, together with population pharmacokinetics(PPK) and pharmacokinetics-pharmacodynamics(PK-PD) analysis. Results confirmed TAZ/PIPC dosage propriety for this group of patients.
1. PPK analysis: Patients with pneumonia were compared to healthy adult volunteers for PIPC and TAZ PK parameters. Systemic clearance was lower and the half-life (t1/2) was longer in those with pneumonia than in healthy volunteers. The steady-state volume of distribution (V) of TAZ in patients with pneumonia was 1.23 times and of PIPC 1.30 times as large as those in healthy adult volunteers. Cmax in blood was lower in patients with pneumonia.
2. Clinical effect: Response three days after treatment was 11.6% (5/43 patients) and time to completion/discontinuation of treatment was 86.0% (37/43 patients). Improvement seven days after completion of treatment was 81.4% (35/43 patients).
3. PK-PD analysis: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis were detected in 24 patients, and all cases were judged to have "disappeared." Calculated time above MIC (%) was 100% in all cases but one (94.6%). When TAZ/PIPC was administered three times a day (4.5 g×3) or four times a day (4.5 g×4) to patients with pneumonia whose Ccr was 120 mL/min, MIC allowing time above MIC (%) exceeding 30% were 32 μg/mL and 64 μg/mL.
4. Safety: Drug-related adverse events numbering 54 were recognized in 24 patients, i.e., an incidence of 40.0%. Of laboratory test abnormalities, 32 adverse events recognized in 16 patients were regarded as drug-related i.e., an incidence of 26.7%.
Given these results, the appropriate TAZ/PIPC dosage adopted for treatment of community-acquired pneumonia is three times daily at 4.5 g.
Key word
tazobactam/piperacillin, community acquired pneumonia, population pharmacokinetics, PK-PD, clinical trial
Received
June 10, 2009
Accepted
December 8, 2009
Jpn. J. Chemother. 58 (S-1): 11-28, 2010
