The correlation between predicted and measured patient specific analgesic concentrations after intravenous titration: a guide for initial maintenance requirements with methadone.

The relationship between the analgesic methadone concentrations measured and those predicted using a pharmacokinetic approach were assessed in 22 patients referred for long-term management of severe pain with intravenous methadone. Five milligrams of methadone were administered IV every 10 minutes until the patient reported a visual analog scale (VAS) pain score of less than or equal to 2. Initial maintenance infusion rates were chosen based on the number of 5 mg doses required to produce satisfactory analgesia. Overall, the methadone concentrations predicted using pharmacokinetic modeling were in excellent agreement with those actually measured. Over 95% of the variance in the data was explained using this model (r2 = 0.9704). Using the rapid titration paradigm described here, one can obtain a reasonable estimate of patient specific analgesic (target) concentration as well as initial infusion requirements for methadone.

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 concentration-time 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 less than 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 less than 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, methadone CL is markedly elevated while the Vc is essentially unchanged during the early post burn injury period.(ABSTRACT TRUNCATED AT 250 WORDS)