Clinical pharmacological study of tazobactam/piperacillin in patients with community-acquired pneumonia

Akira Watanabe, Nobuki Aoki, Yoshihito Niki, Atsushi Saito, Shigeru Kohno, Kohya Shiba

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    6 Citations (Scopus)

    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 x 3) or four times a day (4.5 g x 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 drugrelated 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.

    Original languageEnglish
    Pages (from-to)11-28
    Number of pages18
    JournalJapanese Journal of Chemotherapy
    Volume58
    Issue numberSUPPL. 1
    Publication statusPublished - 2010 Mar 1

    Keywords

    • Clinical trial
    • Community acquired pneumonia
    • PK-PD
    • Population pharmacokinetics
    • Tazobactam/piperacillin

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmacology (medical)

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  • Cite this

    Watanabe, A., Aoki, N., Niki, Y., Saito, A., Kohno, S., & Shiba, K. (2010). Clinical pharmacological study of tazobactam/piperacillin in patients with community-acquired pneumonia. Japanese Journal of Chemotherapy, 58(SUPPL. 1), 11-28.