Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications

Abstract

Background: Methamphetamine is one of the most toxic of the drugs of abuse, which may reflect its distribution and accumulation in the body. However no studies have measured methamphetamine's organ distribution in the human body.

Methods: Positron Emission Tomography (PET) was used in conjunction with [(11)C]d-methamphetamine to measure its whole-body distribution and bioavailability as assessed by peak uptake (% Dose/cc), rate of clearance (time to reach 50% peak-clearance) and accumulation (area under the curve) in healthy participants (9 Caucasians and 10 African Americans).

Results: Methamphetamine distributed through most organs. Highest uptake (whole organ) occurred in lungs (22% Dose; weight ∼1246 g), liver (23%; weight ∼1677 g) and intermediate in brain (10%; weight ∼1600 g). Kidneys also showed high uptake (per/cc basis) (7%; weight 305 g). Methamphetamine's clearance was fastest in heart and lungs (7-16 minutes), slowest in brain, liver and stomach (>75 minutes), and intermediate in kidneys, spleen and pancreas (22-50 minutes). Lung accumulation of [(11)C]d-methamphetamine was 30% higher for African Americans than Caucasians (p<0.05) but did not differ in other organs.

Conclusions: The high accumulation of methamphetamine, a potent stimulant drug, in most body organs is likely to contribute to the medical complications associated with methamphetamine abuse. In particular, we speculate that methamphetamine's high pulmonary uptake could render this organ vulnerable to infections (tuberculosis) and pathology (pulmonary hypertension). Our preliminary findings of a higher lung accumulation of methamphetamine in African Americans than Caucasians merits further investigation and questions whether it could contribute to the infrequent use of methamphetamine among African Americans.

Figure 1. Averaged time-activity curves of [¹¹C]d-metamphetamine in the various organs of the body.

Note that the values correspond to the average for all subjects (AA and C) whereas Table 2 reports separate values for AA and C, which is why they don't exactly match.

Figure 2. Whole body images of [¹¹C]d-methamphetamine in an African American (AA) and in a Caucasian (C) who received 7.18 and 6.99 mCi respectively and location of areas where ROI were obtained.

Imaging was started 4 min post injection moving from head to pelvis in 12 minute segments. The images have been decay corrected. Note the higher accumulation of [¹¹C]d-methamphetamine in the lung of the AA than of the C. The hot spot on the abdominal cavity of the Caucasian corresponds to the stomach where [¹¹C]d-methamphetamine accumulation was high but quite variable across subjects (may reflect its acidic environment that favors trapping of methamphetamine, which is a weak base).