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Urinary Pharmacokinetics of Methamphetamine and Its Metabolite, Amphetamine Following Controlled Oral Administration to Humans

Kim, Insook PhD*‡; Oyler, Jonathan M. BA*‡; Moolchan, Eric T. MD*; Cone, Edward J. PhD; Huestis, Marilyn A. PhD*

Original Article
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Methamphetamine is widely abused for its euphoric effects. Our objectives were to characterize the urinary pharmacokinetics of methamphetamine and amphetamine after controlled methamphetamine administration to humans and to improve the interpretation of urine drug test results. Participants (n = 8) received 4 daily 10-mg (low) oral doses of sustained-release (d)-methamphetamine hydrochloride within 7 days. After 4 weeks, 5 participants received 4 daily 20-mg (high) oral doses. All urine specimens were collected during the study. Methamphetamine and amphetamine were measured by GC-MS/PCI. Maximum excretion rates ranged from 403 to 4919 μg/h for methamphetamine and 59 to 735 μg/h for amphetamine with no relationship between dose and excretion rate. The mean molar percentage of dose in the urine as total methamphetamine and amphetamine were 57.5 ± 21.7% (low dose) and 40.9 ± 8.5% (high dose). Mean urinary terminal elimination half-lives across doses were 23.6 ± 6.6 hours for methamphetamine and 20.7 ± 7.3 hours for amphetamine. Methamphetamine renal clearance across doses was 175 ± 102 mL/min. The mean amphetamine/methamphetamine percentage ratio based on the area under the urinary excretion-time curve increased over time from 13.4 ± 6.5% to 35.7 ± 26.6%. Slow urinary excretion results in drug accumulation and increases in detection time windows. Our findings also support the presence of an active renal excretion mechanism for methamphetamine.

From the *Chemistry and Drug Metabolism Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD; and †ConeChem Research, 441 Fairtree Drive, Severna Park, MD.

Received for publication November 14, 2003; accepted May 17, 2004.

‡These authors contributed equally to this work.

This study was supported by National Institute on Drug Abuse Intramural Research Funds.

Reprints: Marilyn A. Huestis, PhD, National Institute on Drug Abuse/Intramural Research Program, NIH, Bldg C, Room 371, 5500 Nathan Shock Drive, Baltimore, MD 21224 (e-mail: mhuestis@intra.nida.nih.gov).

© 2004 Lippincott Williams & Wilkins, Inc.