TY - JOUR
T1 - Clinical pharmacological study of tazobactam/piperacillin in patients with community-acquired pneumonia
AU - Watanabe, Akira
AU - Aoki, Nobuki
AU - Niki, Yoshihito
AU - Saito, Atsushi
AU - Kohno, Shigeru
AU - Shiba, Kohya
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/3
Y1 - 2010/3
N2 - 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.
AB - 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.
KW - Clinical trial
KW - Community acquired pneumonia
KW - PK-PD
KW - Population pharmacokinetics
KW - Tazobactam/piperacillin
UR - http://www.scopus.com/inward/record.url?scp=77950792714&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77950792714&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:77950792714
VL - 58
SP - 11
EP - 28
JO - Japanese Journal of Chemotherapy
JF - Japanese Journal of Chemotherapy
SN - 1340-7007
IS - SUPPL. 1
ER -