Serum piperacillin/tazobactam pharmacokinetics in a morbidly obese individual.
OBJECTIVE
To report pharmacokinetic alterations and optimal dosing of piperacillin/tazobactam in an obese patient.


METHODS
A 39-year-old morbidly obese (weight 167 kg, body mass index 50 kg/m2) man was treated with piperacillin/tazobactam 3.375 g every 4 hours for recurrent cellulitis. The wound culture grew Groups A and B Streptococcus and rare Pseudomonas aeruginosa. Blood samples were obtained at steady-state from a peripheral venous catheter at 0, 0.5, 1, 2, 3, and 4 hours after the start of the infusion. Population pharmacokinetics were generated from a previously published data set. The serum concentrations of piperacillin/tazobactam obtained in the patient were compared with the 95% confidence interval from the representative population. Pharmacokinetic parameters such as maximal serum concentration, minimal serum concentration, average steady-state concentration, half-life, elimination rate constant, volume of distribution (V(d)), clearance, area under the curve at steadystate, and percent of time greater than the minimum inhibitory concentration (%t>MIC) were calculated and qualitatively compared between the sample and the population.


CONCLUSIONS
Substantial differences were noted in both the absolute values at the times of sample collection and the overall concentration-versus-time profile of both compounds. The morbidly obese individual compared with the population demonstrated a reduced average serum steady-state concentration: 39.8 mg/L versus 123.6 mg/L, an increased V(d): 54.3 L versus 12.7 L, and an increased half-life: 1.4 hours versus 0.6 hours, respectively. The %t >MIC of piperacillin for the patient, assuming MICs of 2, 4, 8, 16, 32, 64, and 128 mg/L, was 100%, 100%, 90.9%, 55.4%, 19.9%, 0%, and 0%, respectively.


CONCLUSIONS
Pathogens with elevated MICs may require altered dosing schemes with piperacillin/tazobactam. Future studies are warranted to assess increased dosages, more frequent dosing intervals, or continuous infusion dosing schemes for obese individuals with serious infections.
Newman
Diane
D
Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL 60611, USA.
Scheetz
Marc H
MH
Adeyemi
Oluwadamilola A
OA
Montevecchi
Mauro
M
Nicolau
David P
DP
Noskin
Gary A
GA
Postelnick
Michael J
MJ
D000328:Adult; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D009767:Obesity, Morbid / Q000188:drug therapy* / Q000378:metabolism; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010878:Piperacillin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000078142:Tazobactam
D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin