Piperacillin is generally available in their stable form as crystallized potassium or sodium salt, quickly losing bactericidal activity upon dissolution due to their short half-lives. As the gastrointestinal tract does not absorb piperacillin and tazobactam, they are dissolved in a solution before being administered to a patient, through parenteral means. Excreted through renal mechanisms like glomerular or tubular filtration as a component of urine, uncontrolled dosages of the drug can cause renal dysfunction and competitive inhibition of excretion, delaying piperacillin-tazobactam excretion, and endangering patients to drug exposure.
Although the distribution of the drug remained the same, the half-life for elimination increased by three to five folds for patients diagnosed with renal dysfunction. Measured by creatinine clearance (CrCl), patients with less than 30 mL/min of clearance had significantly reduced levels of piperacillin/tazobactam excretion, measuring down to 35% of the initial dosage, while the area under the curve (AUC) for piperacillin increased by about three folds for those with less than 20 mL/min. A reduced dosage or alteration in the interval of administration is recommended for patients lying under 40 mL/min of CrCl, depending on the severity of dysfunction.
Renal is the main pathway for drug elimination for both tazobactam and piperacillin in the body. While there are other non-renal means of drug elimination like hepatobiliary excretion, they occur less frequently. A substantial amount (~80%) of piperacillin found in urine when excreted through glomerular and tubular filtration is unmetabolized. Tazobactam renal elimination may be significantly reduced through piperacillin interaction, dropping from 63.7% to 56.8% of the administered dose over a 24-hour period. Piperacillin may be actively diffused through filtration into the biliary tract during renal clearing, indicated by a generally higher concentration of piperacillin than tazobactam in the bile. The metabolites that make up the remaining percentage in the excreted urine are composed of M1 (inactive) and N-desethyl-piperacillin (active), formed from the division of β-lactam rings of both tazobactam and piperacillin respectively.
Due to the hydrophilic nature of piperacillin-tazobactam, a volume distribution of ~15 L amounting to various sites (tissues) is desired, as hydrophilic compounds are not able to pass through plasma membranes as easily as hydrophobic compounds. Concentrations often in the range of 90 MIC or above are located in specific areas including the gallbladder, lung, muscle, and skin, making up 16–85% of the plasma concentrations. The concentration of piperacillin-tazobactam is especially lower in fatty tissue, making up less than 10% of the plasma concentrations.