Metabolism
- Methamphetamine is demethylated (R-N-CH3 → R-N-H) by CYP2D6 to amphetamine--an active metabolite.
- The remaining metabolic pathways are similar to the pathways seen in amphetamine alone.
Methamphetamine has a half-life of approximately 10 hours depending on urinary pH and can be detected in urine for about 2 days after consumption.
Interpretation
- Both methamphetamine and amphetamine are detected in patients taking methamphetamine.
- Between 30-54% of an oral dose is excreted in urine as unchanged methamphetamine and 10-23% as unchanged amphetamine (approximately 3:1 ratio). Following an intravenous dose, 45% is excreted as unchanged parent drug and 7% as amphetamine (approximately 6:1 ratio). These ratios, of course, depend on many factors, such as urine pH, polymorphisms, and concurrent consumption of inhibitors or inducers of CYP2D6. Dosage and time of dosage can also affect the ratio.
- A urine sample that contains amphetamine at a concentration greater than methamphetamine is not consistent with methamphetamine use alone. It could be the result of drugs such as benzphetamine or mixed use of amphetamine and methamphetamine. Some drugs are actually metabolized to amphetamine and methamphetamine. A couple of examples are benzphetamine and selegeline, a drug used to treat Parkinson's disease. Seligiline is converted to l-methamphetamine and l-amphetamine and benzphetamine is converted to d-methamphetamine and d-amphetamine.
- To further confound interpretation, methamphetamine exists as two isomers, d-methamphetamine and l-methamphetamine. The d-isomer is the illicit form of the drug while the l- isomer is found in over-the-counter medications such as Vick's inhaler.
Occasionally, when a patient has taken meth, the amphetamine metabolite will be present at a level below the cutoff of the laboratories amp confirmation. For example, a patient screens positive for amphetamines by immunoassay, and an amp drug confirmation is reflexed. Methamphetamine is detected at 975 ng/mL and amphetamine at 190 ng/mL. If the laboratory's confirmation cutoff for amps is 200 ng/mL, they will report methamphetamine as positive and amphetamine as negative. This can be confusing to a physician expecting to see the amphetamine metabolite as well as methamphetamine.
To make things more confusing, lets’s say this patient was a “poor metabolizer,” had a prescription for a drug that inhibits CYP2D6, or both. He could have very high levels of methamphetamine and the levels of amphetamine could be very low or below the cutoff. Physicians expecting to see the typical methamphetamine to amphetamine ratio of about 3:1 to 6:1 would be perplexed indeed.
