Vol.61 No.5 September 2013
Pharmacokinetics during repeated administration of tazobactam/piperacillin (TAZ/PIPC) in patients undergoing maintenance hemodialysis
1)Department of Pharmacy Services, Shirasagi Hospital, 7-11-23 Kumata, Higashisumiyoshi-ku, Osaka, Japan
2)Department of Medicine, Shirasagi Hospital
Abstract
No studies have reported the pharmacokinetics of tazobactam/piperacillin(TAZ/PIPC), a penicillin antibiotic combined with a β-lactamase inhibitor at a TAZ/PIPC ratio of 1:8, in Japanese patients with chronic kidney disease on hemodialysis(HD). We intravenously injected a TAZ/PIPC dose of 4.5 g over a 30-min period every 12 h(4.5 g twice daily) to five HD patients diagnosed as having pneumonia or suspected sepsis (one male, four females; mean [±SD] age, 73.2 [9.3] years; mean [±SD] body weight, 46.2 [10.3] kg), and analyzed the pharmacokinetics of TAZ and PIPC using the one-compartment model. Based on the results of the analysis, the proportion of the time during which the plasma PIPC concentration (total concentration, free concentration) was maintained above the minimum inhibitory concentration(MIC)(time above MIC; %TAM) was calculated. The maximum concentrations (Cmax) of TAZ and PIPC after the first administration were 37.5±9.3 and 386±121 μg/mL, respectively. The Cmax values of TAZ and PIPC after repeated administration (4 to 6 days) were 85.1±16.4 and 824±260 μg/mL, respectively, which were both higher than the Cmax after the first administration. The half-lives (T1/2) of TAZ and PIPC were 14.8±5.5 and 10.0±4.1 h, respectively, indicating a markedly delayed elimination compared to individuals with normal renal function. The rate of reduction in plasma concentrations before and after HD was high at 84.0±4.5% for TAZ and 85.4±4.3% for PIPC. Based on the finding that the MIC allowing%TAM exceeding 50% was 64 μg/mL in the four patients in whom pharmacokinetics could be assessed, and taking into consideration the Cmax at which tolerability has been confirmed in other studies, administration of TAZ/PIPC at 4.5 g once daily or 2.25 g twice daily was proposed as an appropriate dose for HD patients. Moreover, with the exception of one patient for whom an assessment could not be made, treatment was effective in the other four patients, and no side effects were observed.
Key word
tazobactam/piperacillin, chronic renal failure, hemodialysis, pharmacokinetics
Received
February 12, 2013
Accepted
June 25, 2013
Jpn. J. Chemother. 61 (5): 427-434, 2013
