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Serum Piperacillin/Tazobactam Pharmacokinetics in a Morbidly Obese Individual

Pharmacy Resident, Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL

Marc H Scheetz, PharmD MSc

Assistant Professor of Pharmacy Practice, College of Pharmacy, Midwestern University, Chicago; Infectious Diseases Pharmacist, Department of Pharmacy, Northwestern Memorial Hospital

Oluwadamilola A Adeyemi, MD

Infectious Diseases Fellow, Department of Medicine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, and Northwestern Memorial Hospital

Mauro Montevecchi, MD

Internal Medicine Resident, Department of Medicine, Feinberg School of Medicine, Northwestern University, and Northwestern Memorial Hospital

David P Nicolau, PharmD FCCP

Director, Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT

Gary A Noskin, MD

Associate Professor, Department of Medicine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, and Northwestern Memorial Hospital

Michael J Postelnick, BSPharm BCPS

Clinical Coordinator, Department of Pharmacy, Northwestern Memorial Hospital

Reprints: Dr. Scheetz, Northwestern Memorial Hospital, 251 E. Huron St., Feinberg Pavilion LC 700, Chicago, IL 60611, fax 312/926-7956, mscheetz{at}nmh.org

OBJECTIVE: To report pharmacokinetic alterations and optimal dosing of piperacillin/tazobactam in an obese patient.

CASE SUMMARY: 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.

DISCUSSION: 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.

Key Words: morbid obesity, piperacillin/tazobactam

Published Online, August 28, 2007. www.theannals.com, DOI 10.1345/aph.1K256