The half-life of a drug is a measure of the time required for the blood concentration of the drug to be reduced by one-half. The half-life of any drug is a function of the rate at which it is metabolized and/or excreted from the body. Methadone is metabolized by the liver. Any condition or drug which blocks or slows the rate of metabolism will increase the half life of Methadone in the blood. As the half-life increases, the Methadone residual in the blood when the next daily dose is administered is higher. This is the same as an increase in the daily dose and may result in symptoms of excess opiate such as central nervous system depression, somnolence, sedation, and respiratory depression. Since Methadone also is excreted in the urine, any condition which causes a decrease in urinary excretion results in an increased accumulation of Methadone in the body as well as increased urine pH. The consequence is the same as increasing the dose. Any condition which results in an acid urine will increase urinary excretion of Methadone. Either of these conditions can destabilize a patient whose dose has not changed.


The ability of the liver to metabolize opiate drugs increases as a result of chronic opiate

use. This process contributes to the tolerance to Methadone manifest by patients dependent upon opiate drugs. Because of the rapid metabolic disposition, the duration of effectiveness of a single dose of Methadone is reduced and withdrawal discomfort occurs sooner. Some drugs other than opiates are capable of inducing enzymes which metabolize Methadone. These drugs are called inducers. Examples of these drugs include some antitubercular preparations, seizure medications and intravenous antibiotics. A stable patient will experience withdrawal symptoms when started on these drugs. Starting during the second trimester and continuing into the third trimester of pregnancy, there is a change in blood protein in the mother which results in reduced availability of Methadone to body organs. This phenomenon commonly causes withdrawal symptoms requiring an increased dose of Methadone. Reduction in dose of Methadone after delivery is usually required.


After an oral dose of Methadone, the blood level peaks two and four hours, and then decreases at a rate determined by the half-life which is in turn determined by the dispositional metabolism. The half-life is highly variable, from 15 to 55 hours. Most patients on Methadone maintenance will have a half-life of 16-24 hours. The blood level falls to about half of the peak level prior to the next dose about 24 hours later. The dose must be controlled so that that peak level does not cause drowsiness and the 24-hour level is not low enough to cause withdrawal discomfort. If a patient is a rapid metabolizer with a half-life of 12 hours, withdrawal symptoms may occur before 24 hours. When the dose is increased to prevent withdrawal between doses, the peak may be so high as to cause drowsiness. This situation may be helped by splitting the dose, which permits reduction of the difference between the high and low blood levels.




A second type of tolerance is cellular tolerance. This occurs when the body adapts to the presence of opiates so that normal functioning persists at abnormally high blood levels of Methadone. This allows a stable Methadone maintained patient to function normally when the blood concentration is several times that which would be fatal to a patient who is not dependent on opiate drugs. Because of cellular tolerance, Methadone blood levels determined by medical examiners cannot by themselves be used to determine cause of death.


The daily Methadone dose of patients who are stable and have both cellular and dispositional tolerance is potentially fatal to those who have not developed tolerance. Deaths have occurred from ingestion of a single dose when ingested by a non-tolerant person.




A third type of tolerance is behavioral. This is learned behavior exercised by a manipulative patient in order to obtain higher doses of Methadone than required for adequate control of withdrawal and craving. This behavior has resulted in death from Methadone excess.


All three types of tolerance - dispositional, cellular and behavioral occur with opiates, alcohol and sedative hypnotic drugs. A patient using solely non-opiate drugs does not qualify for Methadone treatment and may be seriously injured if allowed into Methadone treatment.


These principles are applied during intake procedures designed to verify that a patient qualifies for Methadone treatment by virtue of opiate drug use and by the titration procedure which would identify a non-opiate user by sedation occurring at low doses early in the titration procedure.


Because of the many variables in response to Methadone, neither the dose administered nor the blood level achieved is the target to be reached. The proper dose is that which allows normal functioning, and minimizes craving and drug-seeking behavior. Abundant literature supports that a higher dose range as determined by the tolerance of the patient is associated with an improved treatment outcome as measured by retention, reduced used of other opiates, and improved functioning in the community.




Often, patients who are opiate users and qualify for Methadone maintenance treatment are using other drugs excessively and may be dependent on alcohol, barbiturates, benzodiazepines, or other licit or illicit substances, withdrawal from which could be life-threatening. Special precautions must be taken to prevent sudden abrupt discontinuation of other drugs. The opiate use should be addressed first and other drug use attended to after initial stabilization on Methadone. Withdrawal from non-opiate drugs too rapidly may be life-threatening.




Treatment outcome is strongly influenced by staff attitudes toward patients and by a strong belief in Methadone maintenance treatment. Staff must use reasonable and rational authority toward patients. The patients are viewed as persons and patients, not as clinic numbers. Patients deserve empathy, consideration and respect from the staff. Respect for the staff is demanded and no form of abuse by the patients will be tolerated.


The staff must not have unreasonable rescue fantasies which result in retention of a patient beyond the point where Methadone maintenance modality must be conceded as ineffective. The staff must not be manipulated into allowing concessions outside of current rules and regulations under which the program is permitted to operate. In a private program, the staff is employed by the patients, and patients have the right to expect the staff to be their advocate as long as reasonable engagement in treatment is manifest.