Journal
JOURNAL OF CLINICAL PHARMACOLOGY
Volume 47, Issue 6, Pages 674-680Publisher
WILEY
DOI: 10.1177/0091270007299756
Keywords
pharmacokinetics; cardiac index; hepatic blood flow; opiates
Categories
Funding
- NCCIH NIH HHS [AT-01381] Funding Source: Medline
- NCRR NIH HHS [RR-00054] Funding Source: Medline
- NIA NIH HHS [AG-17780] Funding Source: Medline
- NIDA NIH HHS [DA-05258] Funding Source: Medline
- NIGMS NIH HHS [GM 31569, R01 GM055082, GM 55082] Funding Source: Medline
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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-mu g 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 comportment volume (V-1, 0.37 vs 0.61 L/kg), and total volume of distribution (V-area, 3.6 vs 5.8 L/kg) were higher in burned patients. Cardiac index was unrelated to CL. The increased V-1 and V-area are likely due to large intravenous fluid replacement and tissue edema. Higher CL and larger V-1 and V-area leading to a lower fentanyl plasma concentration may partially explain the increased opiate requirement previously observed after burn injury.
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