Effects of treatment and the metabolic response to injury on drug clearance: a prospective study with piperacillin
Shikuma, L.R.; Ackerman, B.H.; Weaver, R.H.; Solem, L.D.; Strate, R.G.; Cerra, F.B.; Zaske, D.E.
Critical Care Medicine 18(1): 37-41
1990
ISSN/ISBN: 0090-3493 PMID: 2293966 Document Number: 355410
The disposition of piperacillin was prospectively evaluated in 11 critically ill surgical patients who had no evidence of pre-existing renal and hepatic disease. Interpatients variations were demonstrated in the drug's half-life, distribution volume, and clearance, with values of 1.50 .+-. 2.05 (SD) h, 25.0 .+-. 17.2 L, and 23.8 .+-. 17.2 L/h, respectively. Variations in piperacillin disposition were best explained by serum concentrations of albumin, total protein, and biliribuin, and the amount of urea nitrogen excreted daily in urine. Age and renal function were moderately associated with piperacillin elimination rate and clearance. Altered piperacillin disposition thus appeared to occur as secondary to changes in the patients' physiologic and metabolic state caused by injury-related stress and fluid/colloid therapy. These alterations may necessitate dosage modifications to achieve optimal patient response when treating patients with pipercillin as well as with other similar drugs eliminated via renal and nonrenal routes.