**6. Conclusion**

138 Toxicity and Drug Testing

more generalized epidemic into the community through sexual transmission. In the beginning, less than one percent of HIV victims were females. Now it stands at about 20% and this clearly demonstrates the generalization of the HIV epidemic in Malaysia that began as a concentrated epidemic among drug users. Most of the afflicted females are also wives and spouses of drug users who are themselves HIV positive and not sex workers as many would have expected. There is however evidence for a growing epidemic among sex

For the forty patients studied, their daily dose averaged 57.2 mg and ranged from 20 to 160 mg per day. Median dose was 50 mg per day. The corresponding plasma methadone averaged 281.3 ng/ml. It ranged from 0 to 4634 ng/ml. Daily methadone doses poorly predicted resulting plasma methadone concentrations, a hallmark for a drug metabolized by genetically polymorphic enzymes. Indeed when we measured plasma methadone concentrations in patients who received a fixed 40 mg daily methadone , they varied from 14 ng/ml to 331 ng/ml, a 23-fold difference. It is thus evident that no one dose fits all. As with many drugs used in the management of chronic diseases, methadone doses should be

It is also interesting to note that, despite claims by many physicians that relatively lower doses of methadone would be sufficient for our Malaysian patients, our observation of high withdrawal scores among patients who were maintained at 40 mg daily of methadone would imply this was not so. Severe withdrawal would discourage patients from remaining on treatment and by inference, they will not be retained. Indeed it has consistently been found that a sufficiently high dose of substitution therapy was required for improved outcome (Brady *et al*, 2005). High doses of methadone were significantly more effective in suppressing illicit heroin use and in retaining patients in the program (Family Health International; Mattick *et al*, 2003) and in producing optimum outcomes (Farré *et al*, 2002). Inadequate doses and premature termination are the greatest threats to a successful MMT program in Malaysia. Malaysian doctors may outwardly say that they use lower methadone doses because of their fear for ethnic difference that would put their patients at higher risks for toxicity if they were to use doses as high as those recommended by the Western literature. What they may not want to admit is the fact that, inwardly, they have fears with methadone (and all opiates actually!) just for the simple reason that methadone is an opiate, just like the dreaded heroin and morphine! Indeed Malaysian doctors are not alone in this. Many doctors everywhere share the same view. Thus, despite ample evidence for the need to maintain patients at a daily dose of 80 mg to 100 mg, most patients are maintained on

It is probably understandable that the lay public may not understand the scientific basis for MMT and could be disparaging and become critical of it. It is however less clear why many physicians and other health care providers have the same views. Even those directly involved with MMT programs frequently fail to adhere to the basic principles of MMT. Most have actually received clear information on the pharmacologic principles underlying MMT and their claim that they want to prescribe as few medications as possible sound hollow, as they frequently easily prescribe other mood altering drugs, such as the benzodiazepines that are often prescribed with abandon and can produce psychological and physiologic dependency. Even if they claim they fear adverse effects, the adverse, physiologic effects of MMT are minimal and methadone is probably associated with the least side effects of any drug in a physician's pharmacologic armamentarium, when used appropriately. The real reason is probably more to do with the general "opiophobias" as it is known that some

workers and this again has the potential to generalize into the community.

individualized to optimum outcomes that must be determined objectively.

much less, and many are encouraged early termination.

We concluded that the variable plasma methadone obtained was poorly correlated with daily doses of methadone and low dose methadone was inadequate to suppress opiate withdrawal.

A daily dose of 40 mg was associated with a high incidence of opiate withdrawal. Thus, prescription of methadone dose should be individualised to achieve a higher success of MMT.
