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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.
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Denson et al. (1990) studied this question.
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