Clinical pharmacokinetics of methadone.

Studies with single doses of methadone have shown that the oral biological availability is 79 +/- 21%, range 41-99%. The rate of elimination is mostly due to metabolic clearance. Below a urinary pH of 6, renal clearance becomes of quantitative importance. In five subjects treated with ammonium chloride (acidic urine), the plasma half-life of methadone was found to be 19.5 +/- 3.6 h. When treated with sodium bicarbonate the same subjects had plasma half-lives of 42.1 +/- 8.8 h. During continuous treatment with methadone, cellular tolerance may occur and in some subjects also metabolic tolerance. In treatment of severe cancer pain such adaptive changes in methadone pharmacodynamics and pharmacokinetics are best managed by a regimen involving a fixed dose but a flexible and patient-controlled dosage interval.