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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Pharmacokinetics and tissue penetration of tazobactam and piperacillin in patients undergoing colorectal surgery.

The pharmacokinetics of tazobactam and piperacillin in plasma and different tissues after a 30-min intravenous infusion of 4 g of piperacillin and 0.5 g of tazobactam were investigated in 18 patients who underwent elective colorectal surgery. Serial blood samples were collected for up to 6 h after the initiation of the infusion. The types of tissue collected were fatty tissue, muscle, skin, appendix, and intestinal mucosa (proximal and distal). On the basis of concentrations in plasma, the following pharmacokinetic parameter values were obtained (values are means +/- standard deviations): maximum concentration of drug in serum, tazobactam, 27.9 +/- 7.67 micrograms/ml; piperacillin, 259 +/- 81.8 micrograms/ml; time to maximum concentration of drug in serum, tazobactam, 0.51 +/- 0.03 h; piperacillin, 0.51 +/- 0.03 h; area under the concentration-time curve, tazobactam, 47.6 +/- 13.3 micrograms.h/ml; piperacillin, 361 +/- 80.3 micrograms.h/ml; clearance, tazobactam, 188 +/- 52.3 ml/min; piperacillin, 194 +/- 42.9 ml/min; half-life, tazobactam, 1.42 +/- 0.32 h; piperacillin, 1.27 +/- 0.24 h; apparent volume of distribution, tazobactam, 0.31 +/- 0.07 liter/kg of body weight; piperacillin, 0.29 +/- 0.06 liter/kg; volume of distribution at steady state, tazobactam, 0.28 +/- 0.04 liter/kg; piperacillin, 0.25 +/- 0.05 liter/kg. The concentrations of tazobactam and piperacillin in fatty tissue and muscle tissue were 10 to 13 and 18 to 30% of the levels in plasma, respectively. In skin, the concentrations of piperacillin were 60 to 95% of the levels in plasma, whereas the concentrations of tazobactam in plasma were 49 to 93% of the levels in skin tissue. The mean concentration of tazobactam in the investigated gastrointestinal tissues (appendix, proximal and distal mucosa) exceeded levels in plasma after 1 h, while piperacillin showed a mean penetration into these tissues of 43 and 53%. The mechanisms that can be used to explain the extent of penetration of piperacillin and tazobactam are discussed. Simple diffusion may take place in fatty and muscle tissue, while penetration into skin and gastrointestinal tissue is governed by more complex mechanisms which lead to differences in penetration between piperacillin and tazobactam. For all tissues investigated (except fatty tissue), the time course of the concentrations of both compounds was similar, with a peak in concentration at between 1 and 2 h after the start of infusion followed by a decline of concentrations that were almost parallel to the curves of the drug concentrations in plasma. In plasma and in all investigated tissues, piperacillin as well as tazobactam reached or exceeded the concentrations found to be effective in vitro.[1]


  1. Pharmacokinetics and tissue penetration of tazobactam and piperacillin in patients undergoing colorectal surgery. Kinzig, M., Sörgel, F., Brismar, B., Nord, C.E. Antimicrob. Agents Chemother. (1992) [Pubmed]
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