J Clin Pharmacol
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First published on April 11, 2007, doi:10.1177/0091270007299756

The Journal of Clinical Pharmacology 2007;47:674.

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©© 2007 American College of Clinical Pharmacology, Inc.
The Journal of Clinical Pharmacology , 10.1177/0091270007299756

Article

Fentanyl Clearance and Volume of Distribution Are Increased in Patients With Major Burns

Taehyung Han 1*, Jerold S. Harmatz 2, David J. Greenblatt 2, and J. A. Jeevendra Martyn 3

1 University of Iowa Hospitals and Clinics, Carver College of Medicine
2 Tufts University School of Medicine and Tufts-New England Medical Center
3 Harvard Medical School, Massachusetts General Hospital and Shriners Hospital for Children

* To whom correspondence should be addressed. E-mail: athan{at}unitel.co.kr.


  Abstract
This study examined the pharmacokinetics of fentanyl in burned patients during the hyperdynamic phase. Twenty adults, aged 37 ± 2 years (mean ± SE), with 49 ± 3% total body surface area burn, were studied at 17 ± 2 days after the injury and compared to demographically matched controls. After a 200-µg IV bolus of fentanyl, blood samples (n = 20) were collected for 4.5 hours. Concentration-time curves were fitted to a 2-compartment model. Burned patients had a higher cardiac index. Median fentanyl clearance (CL, 21.0 vs 29.4 mL/kg/min), central compartment volume (V1, 0.37 vs 0.61 L/kg), and total volume of distribution (Varea, 3.6 vs 5.8 L/kg) were higher in burned patients. Cardiac index was unrelated to CL. The increased V1 and Varea are likely due to large intravenous fluid replacement and tissue edema. Higher CL and larger V1 and Varea leading to a lower fentanyl plasma concentration may partially explain the increased opiate requirement previously observed after burn injury.
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T.-H. Han, D. J. Greenblatt, and J. A. J. Martyn
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A. J. Dalley, J. Lipman, R. Deans, B. Venkatesh, M. Rudd, M. S. Roberts, and S. E. Cross
Tissue Accumulation of Cephalothin in Burns: a Comparative Study by Microdialysis of Subcutaneous Interstitial Fluid Cephalothin Concentrations in Burn Patients and Healthy Volunteers
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