PHARMACOKINETICS OF CONTINUOUS INTRAVENOUS-INFUSION OF METHADONE IN THE EARLY POST-BURN PERIOD

The pharmacokinetics of methadone were studied in 14 patients with acute, severe burns and receiving an intravenous infusion of methadone to control their pain. Serum methadone concentrations were measured by gas chromatography on 5 mL arterial blood samples obtained at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0 and 24 hours after the start of infusion. Albumin and Alpha-1-Acid glycoprotein (AAG) were measured by radial immunodiffusion. Serum methadone concentration-time data were fit with the appropriate sum of exponentials equation using iterative nonlinear regression analysis. All serum methadone concentrationt-ime data were best described by a monoexponential equation. Estimates of Vd (180 ± 62 L) were not significantly different from those predicted for Vc from body weight using literature values (156 ± 41). Estimates of Vd were, however, significantly lower than those predicted for Vz using literature values (282 ± 74) (P < 0.001). In addition, CL values (53.0 ± 19.3 L/h) were significantly higher than those predicted from body weight using literature values (9.2 ± 2.3 L/h) (P < 0.001). These changes resulted in estimates of the elimination half-life for methadone of 2.6 ± 1.1 h. Methadone protein binding was independent of both albumin and AAG concentration. Multiple regression demonstrated that the significant predictors of CL in the early post burn injury period were serum albumin, days post injury and age. The coefficient of determination (r2) for this model was 0.8190. In summary, mathadone CL is markedly elevated while the Vc is essentially unchanged during the early post burn injury period. These changes suggest that normal loading doses but increased maintenance doses of methadone should be used during this period to provide prolonged analgesia.