Abstract
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Objectives Methamphetamine, one of the most addictive and toxic of the drugs of abuse, is abused much less frequently by African Americans than by Caucasians. This study explored the possibility that differences in use could result from differences in drug bioavailability that could either decrease its reinforcing effects or increase its side effects.
Methods PET was used to compare the bioavailability of [11C]d-methamphetamine in the organs of the body between Caucasians (n=9) and African Americans (n=10). We quantified peak uptake (% injected dose per cc), rate of clearance (time to reach 50% peak clearance) and organ accumulation (area under the curve) of [11C]d-methamphetamine.
Results [11C]d-Methamphetamine distributed throughout the whole body with the highest peak uptake (% Dose/cc) occurring in lungs and kidneys (0.023-0.017) followed by pancreas, spleen, liver and stomach (0.013-0.015) and the lowest uptake occurring in brain and heart (0.006-0.007). The clearance (half-peak clearance) was fastest for heart and lungs (7-16 min) and slowest for brain, liver and stomach (> 75 minutes). Group comparison showed that the accumulation (area under the curve) of [11C]d-methamphetamine in the lungs was 33% higher in African Americans (0.39 ±0.07) than in Caucasians (0.29 ± 0.08, p < 0.05) but did not differ in the other organs nor were there differences in plasma concentration (metabolized and non-metabolized [11C]d-methamphetamine). As a result, the ratio for the accumulation of [11C]d-methamphetamine in striatum to that in lung was significantly lower in African Americans (0.98 ±0.3) than in Caucasians (1.4 ±0.3; p < 0.05).
Conclusions The high accumulation of methamphetamine in the body likely contributes to its high toxicity and mortality. The higher lung accumulation of methamphetamine in African Americans than in Caucasians could result in greater adverse effects, which may contribute to the lower abuse of methamphetamine in this population.
Research Support NIH and Department of Energ